{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:17:15Z","timestamp":1791951435086,"version":"4.3.4"},"reference-count":359,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007801","name":"Fondazione AriSLA","doi-asserted-by":"publisher","award":["SUMOsolvable"],"award-info":[{"award-number":["SUMOsolvable"]}],"id":[{"id":"10.13039\/501100007801","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007801","name":"Fondazione AriSLA","doi-asserted-by":"publisher","award":["AHA-MCA 2022"],"award-info":[{"award-number":["AHA-MCA 2022"]}],"id":[{"id":"10.13039\/501100007801","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007801","name":"Fondazione AriSLA","doi-asserted-by":"publisher","award":["PNRR-MAD-2022-12375798"],"award-info":[{"award-number":["PNRR-MAD-2022-12375798"]}],"id":[{"id":"10.13039\/501100007801","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007801","name":"Fondazione AriSLA","doi-asserted-by":"publisher","award":["PNRR-MCNT2-2023-12378140"],"award-info":[{"award-number":["PNRR-MCNT2-2023-12378140"]}],"id":[{"id":"10.13039\/501100007801","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Giovanni-Armenise Harvard Foundation","award":["SUMOsolvable"],"award-info":[{"award-number":["SUMOsolvable"]}]},{"name":"Giovanni-Armenise Harvard Foundation","award":["AHA-MCA 2022"],"award-info":[{"award-number":["AHA-MCA 2022"]}]},{"name":"Giovanni-Armenise Harvard Foundation","award":["PNRR-MAD-2022-12375798"],"award-info":[{"award-number":["PNRR-MAD-2022-12375798"]}]},{"name":"Giovanni-Armenise Harvard Foundation","award":["PNRR-MCNT2-2023-12378140"],"award-info":[{"award-number":["PNRR-MCNT2-2023-12378140"]}]},{"name":"European Union\u2014Next Generation EU","award":["SUMOsolvable"],"award-info":[{"award-number":["SUMOsolvable"]}]},{"name":"European Union\u2014Next Generation EU","award":["AHA-MCA 2022"],"award-info":[{"award-number":["AHA-MCA 2022"]}]},{"name":"European Union\u2014Next Generation EU","award":["PNRR-MAD-2022-12375798"],"award-info":[{"award-number":["PNRR-MAD-2022-12375798"]}]},{"name":"European Union\u2014Next Generation EU","award":["PNRR-MCNT2-2023-12378140"],"award-info":[{"award-number":["PNRR-MCNT2-2023-12378140"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Cells"],"abstract":"<jats:p>Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are two neurodegenerative disorders that share common genes and pathomechanisms and are referred to as the ALS-FTD spectrum. A hallmark of ALS-FTD pathology is the abnormal aggregation of proteins, including Cu\/Zn superoxide dismutase (SOD1), transactive response DNA-binding protein 43 (TDP-43), fused in sarcoma\/translocated in liposarcoma (FUS\/TLS), and dipeptide repeat proteins resulting from C9orf72 hexanucleotide expansions. Genetic mutations linked to ALS-FTD disrupt protein stability, phase separation, and interaction networks, promoting misfolding and insolubility. This review explores the molecular mechanisms underlying protein aggregation in ALS-FTD, with a particular focus on TDP-43, as it represents the main aggregated species inside pathological inclusions and can also aggregate in its wild-type form. Moreover, this review describes the protective mechanisms activated by the cells to prevent protein aggregation, including molecular chaperones and post-translational modifications (PTMs). Understanding these regulatory pathways could offer new insights into targeted interventions aimed at mitigating cell toxicity and restoring cellular function.<\/jats:p>","DOI":"10.3390\/cells14100680","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T09:58:09Z","timestamp":1746698289000},"page":"680","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Molecular Mechanisms of Protein Aggregation in ALS-FTD: Focus on TDP-43 and Cellular Protective Responses"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8688-7514","authenticated-orcid":false,"given":"Enza Maria","family":"Verde","sequence":"first","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Secco","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6073-0107","authenticated-orcid":false,"given":"Andrea","family":"Ghezzi","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9244-9782","authenticated-orcid":false,"given":"Jessica","family":"Mandrioli","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0939-0140","authenticated-orcid":false,"given":"Serena","family":"Carra","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1212\/WNL.59.7.1077","article-title":"The Overlap of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia","volume":"59","author":"Anderson","year":"2002","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1080\/21678421.2020.1779298","article-title":"Focus on the Heterogeneity of Amyotrophic Lateral Sclerosis","volume":"21","author":"Bendotti","year":"2020","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2883","DOI":"10.1093\/brain\/aws144","article-title":"Young-Onset Amyotrophic Lateral Sclerosis: Historical and Other Observations","volume":"135","author":"Turner","year":"2012","journal-title":"Brain"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"a024117","DOI":"10.1101\/cshperspect.a024117","article-title":"Clinical Spectrum of Amyotrophic Lateral Sclerosis (ALS)","volume":"7","author":"Grad","year":"2017","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.ncl.2017.01.008","article-title":"Frontotemporal Dementia","volume":"35","author":"Olney","year":"2017","journal-title":"Neurol. Clin."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ragagnin, A.M.G., Shadfar, S., Vidal, M., Jamali, M.S., and Atkin, J.D. (2019). Motor Neuron Susceptibility in ALS\/FTD. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.00532"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/S0140-6736(16)00737-6","article-title":"The Frontotemporal Dementia-Motor Neuron Disease Continuum","volume":"388","author":"Burrell","year":"2016","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5673","DOI":"10.1007\/s12035-022-02934-z","article-title":"Recent Updates on the Genetics of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia","volume":"59","author":"Kirola","year":"2022","journal-title":"Mol. Neurobiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41580-019-0101-y","article-title":"The Proteostasis Network and Its Decline in Ageing","volume":"20","author":"Hipp","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Kinger, S., Dubey, A.R., Kumar, P., Jagtap, Y.A., Choudhary, A., Kumar, A., Prajapati, V.K., Dhiman, R., and Mishra, A. (2023). Molecular Chaperones\u2019 Potential against Defective Proteostasis of Amyotrophic Lateral Sclerosis. Cells, 12.","DOI":"10.3390\/cells12091302"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Perni, M., and Mannini, B. (2024). Targeting Protein Aggregation in ALS. Biomolecules, 14.","DOI":"10.3390\/biom14101324"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Abramzon, Y.A., Fratta, P., Traynor, B.J., and Chia, R. (2020). The Overlapping Genetics of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Front. Neurosci., 14.","DOI":"10.3389\/fnins.2020.00042"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1126\/science.aaa3650","article-title":"Exome Sequencing in Amyotrophic Lateral Sclerosis Identifies Risk Genes and Pathways","volume":"347","author":"Cirulli","year":"2015","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1111\/ene.14393","article-title":"Amyotrophic Lateral Sclerosis: A Clinical Review","volume":"27","author":"Masrori","year":"2020","journal-title":"Eur. J. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/ng.3622","article-title":"Genome-Wide Association Analyses Identify New Risk Variants and the Genetic Architecture of Amyotrophic Lateral Sclerosis","volume":"48","author":"Shatunov","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Wang, H., Guan, L., and Deng, M. (2023). Recent Progress of the Genetics of Amyotrophic Lateral Sclerosis and Challenges of Gene Therapy. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1170996"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.neuron.2013.07.033","article-title":"Converging Mechanisms in ALS and FTD: Disrupted RNA and Protein Homeostasis","volume":"79","author":"Ling","year":"2013","journal-title":"Neuron"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.semcdb.2019.06.003","article-title":"ALS and FTD: Where RNA Metabolism Meets Protein Quality Control","volume":"99","author":"Mandrioli","year":"2020","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"R77","DOI":"10.1093\/hmg\/ddt349","article-title":"Pathological Mechanisms Underlying TDP-43 Driven Neurodegeneration in FTLD-ALS Spectrum Disorders","volume":"22","author":"Janssens","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.neuron.2020.08.022","article-title":"ALS Genetics: Gains, Losses, and Implications for Future Therapies","volume":"108","author":"Kim","year":"2020","journal-title":"Neuron"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1136\/jnnp-2016-315018","article-title":"Genetic Epidemiology of Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis","volume":"88","author":"Zou","year":"2017","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/362059a0","article-title":"Mutations in Cu\/Zn Superoxide Dismutase Gene Are Associated with Familial Amyotrophic Lateral Sclerosis","volume":"362","author":"Rosen","year":"1993","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/sj.onc.1208207","article-title":"CuZnSOD Deficiency Leads to Persistent and Widespread Oxidative Damage and Hepatocarcinogenesis Later in Life","volume":"24","author":"Elchuri","year":"2005","journal-title":"Oncogene"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1016\/j.freeradbiomed.2006.01.036","article-title":"Absence of CuZn Superoxide Dismutase Leads to Elevated Oxidative Stress and Acceleration of Age-Dependent Skeletal Muscle Atrophy","volume":"40","author":"Muller","year":"2006","journal-title":"Free Radic. Biol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1083\/jcb.201708007","article-title":"Superoxide Dismutases: Dual Roles in Controlling ROS Damage and Regulating ROS Signaling","volume":"217","author":"Wang","year":"2018","journal-title":"J. Cell Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.gene.2015.11.049","article-title":"Mutant SOD1 Mediated Pathogenesis of Amyotrophic Lateral Sclerosis","volume":"577","author":"Kaur","year":"2016","journal-title":"Gene"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"15094","DOI":"10.1074\/jbc.M113.542613","article-title":"Dimerization, Oligomerization, and Aggregation of Human Amyotrophic Lateral Sclerosis Copper\/Zinc Superoxide Dismutase 1 Protein Mutant Forms in Live Cells","volume":"289","author":"Kim","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1809592","DOI":"10.1155\/2017\/1809592","article-title":"Relationships between Stress Granules, Oxidative Stress, and Neurodegenerative Diseases","volume":"2017","author":"Chen","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"L\u00e9vy, E., El Banna, N., Ba\u00eflle, D., Heneman-Masurel, A., Truchet, S., Rezaei, H., Huang, M.-E., B\u00e9ringue, V., Martin, D., and Vernis, L. (2019). Causative Links between Protein Aggregation and Oxidative Stress: A Review. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20163896"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.jmb.2012.04.016","article-title":"Early Steps in Oxidation-Induced SOD1 Misfolding: Implications for Non-Amyloid Protein Aggregation in Familial ALS","volume":"421","author":"Mulligan","year":"2012","journal-title":"J. Mol. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1093\/hmg\/10.19.2013","article-title":"Oxidative Stress Causes Abnormal Accumulation of Familial Amyotrophic Lateral Sclerosis-Related Mutant SOD1 in Transgenic Caenorhabditis Elegans","volume":"10","author":"Oeda","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"47551","DOI":"10.1074\/jbc.M207356200","article-title":"Oxidation-Induced Misfolding and Aggregation of Superoxide Dismutase and Its Implications for Amyotrophic Lateral Sclerosis","volume":"277","author":"Rakhit","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.neuron.2011.09.011","article-title":"Expanded GGGGCC Hexanucleotide Repeat in Noncoding Region of C9ORF72 Causes Chromosome 9p-Linked FTD and ALS","volume":"72","author":"Mackenzie","year":"2011","journal-title":"Neuron"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.neuron.2011.09.010","article-title":"A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTD","volume":"72","author":"Renton","year":"2011","journal-title":"Neuron"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Smeyers, J., Banchi, E.-G., and Latouche, M. (2021). C9ORF72: What It Is, What It Does, and Why It Matters. Front. Cell. Neurosci., 15.","DOI":"10.3389\/fncel.2021.661447"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1038\/s41582-018-0047-2","article-title":"C9orf72-Mediated ALS and FTD: Multiple Pathways to Disease","volume":"14","author":"Balendra","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/nature13124","article-title":"C9orf72 Nucleotide Repeat Structures Initiate Molecular Cascades of Disease","volume":"507","author":"Haeusler","year":"2014","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/nm.4490","article-title":"Haploinsufficiency Leads to Neurodegeneration in C9ORF72 ALS\/FTD Human Induced Motor Neurons","volume":"24","author":"Shi","year":"2018","journal-title":"Nat. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/j.neurobiolaging.2014.09.012","article-title":"Characterization of DNA G-Quadruplex Species Forming from C9ORF72 G4C2-Expanded Repeats Associated with Amyotrophic Lateral Sclerosis and Frontotemporal Lobar Degeneration","volume":"36","author":"Pohleven","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"8272","DOI":"10.1038\/s41467-023-43872-1","article-title":"The ALS\/FTD-Related C9orf72 Hexanucleotide Repeat Expansion Forms RNA Condensates through Multimolecular G-Quadruplexes","volume":"14","author":"Raguseo","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.neuron.2013.02.004","article-title":"Unconventional Translation of C9ORF72 GGGGCC Expansion Generates Insoluble Polypeptides Specific to C9FTD\/ALS","volume":"77","author":"Ash","year":"2013","journal-title":"Neuron"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"E4968","DOI":"10.1073\/pnas.1315438110","article-title":"RAN Proteins and RNA Foci from Antisense Transcripts in C9ORF72 ALS and Frontotemporal Dementia","volume":"110","author":"Zu","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1038\/nn.3230","article-title":"Divergent Roles of ALS-Linked Proteins FUS\/TLS and TDP-43 Intersect in Processing Long Pre-MRNAs","volume":"15","author":"Polymenidou","year":"2012","journal-title":"Nat. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6030","DOI":"10.1073\/pnas.1203028109","article-title":"TLS\/FUS (Translocated in Liposarcoma\/Fused in Sarcoma) Regulates Target Gene Transcription via Single-Stranded DNA Response Elements","volume":"109","author":"Tan","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1038\/nn.3514","article-title":"Interaction of FUS and HDAC1 Regulates DNA Damage Response and Repair in Neurons","volume":"16","author":"Wang","year":"2013","journal-title":"Nat. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.cell.2017.08.048","article-title":"Structure of FUS Protein Fibrils and Its Relevance to Self-Assembly and Phase Separation of Low-Complexity Domains","volume":"171","author":"Murray","year":"2017","journal-title":"Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.cell.2015.07.047","article-title":"A Liquid-to-Solid Phase Transition of the ALS Protein FUS Accelerated by Disease Mutation","volume":"162","author":"Patel","year":"2015","journal-title":"Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1186\/s40478-016-0358-8","article-title":"Pathogenesis of FUS-Associated ALS and FTD: Insights from Rodent Models","volume":"4","author":"Nolan","year":"2016","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"15635","DOI":"10.1074\/jbc.M111.333450","article-title":"TDP-43 and FUS RNA-Binding Proteins Bind Distinct Sets of Cytoplasmic Messenger RNAs and Differently Regulate Their Post-Transcriptional Fate in Motoneuron-like Cells","volume":"287","author":"Colombrita","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1111\/nan.12148","article-title":"Loss of Nuclear TDP-43 in Amyotrophic Lateral Sclerosis (ALS) Causes Altered Expression of Splicing Machinery and Widespread Dysregulation of RNA Splicing in Motor Neurones","volume":"40","author":"Highley","year":"2014","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"R46","DOI":"10.1093\/hmg\/ddq137","article-title":"TDP-43 and FUS\/TLS: Emerging Roles in RNA Processing and Neurodegeneration","volume":"19","author":"Polymenidou","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"20329","DOI":"10.1074\/jbc.M109.010264","article-title":"TDP-43 Is Intrinsically Aggregation-Prone, and Amyotrophic Lateral Sclerosis-Linked Mutations Accelerate Aggregation and Increase Toxicity","volume":"284","author":"Johnson","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1016\/j.str.2016.07.007","article-title":"ALS Mutations Disrupt Phase Separation Mediated by \u03b1-Helical Structure in the TDP-43 Low-Complexity C-Terminal Domain","volume":"24","author":"Conicella","year":"2016","journal-title":"Structure"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Lim, L., Wei, Y., Lu, Y., and Song, J. (2016). ALS-Causing Mutations Significantly Perturb the Self-Assembly and Interaction with Nucleic Acid of the Intrinsically Disordered Prion-Like Domain of TDP-43. PLoS Biol., 14.","DOI":"10.1371\/journal.pbio.1002338"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/s41583-021-00431-1","article-title":"Triad of TDP43 Control in Neurodegeneration: Autoregulation, Localization and Aggregation","volume":"22","author":"Tziortzouda","year":"2021","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Prasad, A., Bharathi, V., Sivalingam, V., Girdhar, A., and Patel, B.K. (2019). Molecular Mechanisms of TDP-43 Misfolding and Pathology in Amyotrophic Lateral Sclerosis. Front. Mol. Neurosci., 12.","DOI":"10.3389\/fnmol.2019.00025"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"eabb3774","DOI":"10.1126\/scitranslmed.abb3774","article-title":"C9orf72 Poly(GR) Aggregation Induces TDP-43 Proteinopathy","volume":"12","author":"Cook","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1126\/science.1232927","article-title":"The C9orf72 GGGGCC Repeat Is Translated into Aggregating Dipeptide-Repeat Proteins in FTLD\/ALS","volume":"339","author":"Mori","year":"2013","journal-title":"Science"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1080\/15548627.2019.1644076","article-title":"ALS-FTLD-Linked Mutations of SQSTM1\/P62 Disrupt Selective Autophagy and NFE2L2\/NRF2 Anti-Oxidative Stress Pathway","volume":"16","author":"Deng","year":"2020","journal-title":"Autophagy"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"5391","DOI":"10.1007\/s10072-022-06125-5","article-title":"OPTN Variants in ALS Cases: A Case Report of a Novel Mutation and Literature Review","volume":"43","author":"Mou","year":"2022","journal-title":"Neurol. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/s00401-013-1090-0","article-title":"Mutations in SQSTM1 Encoding P62 in Amyotrophic Lateral Sclerosis: Genetics and Neuropathology","volume":"125","author":"Teyssou","year":"2013","journal-title":"Acta Neuropathol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.brainres.2016.03.032","article-title":"Proteostasis Impairment in ALS","volume":"1648","author":"Ruegsegger","year":"2016","journal-title":"Brain Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"jcs209122","DOI":"10.1242\/jcs.209122","article-title":"SOD1A4V Aggregation Alters Ubiquitin Homeostasis in a Cell Model of ALS","volume":"131","author":"Farrawell","year":"2018","journal-title":"J. Cell Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"101700","DOI":"10.1016\/j.isci.2020.101700","article-title":"Ubiquitin Homeostasis Is Disrupted in TDP-43 and FUS Cell Models of ALS","volume":"23","author":"Farrawell","year":"2020","journal-title":"iScience"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"113160","DOI":"10.1016\/j.celrep.2023.113160","article-title":"Analysis of Proteome-Wide Degradation Dynamics in ALS SOD1 IPSC-Derived Patient Neurons Reveals Disrupted VCP Homeostasis","volume":"42","author":"Tsioras","year":"2023","journal-title":"Cell Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.cell.2017.12.030","article-title":"In Situ Structure of Neuronal C9orf72 Poly-GA Aggregates Reveals Proteasome Recruitment","volume":"172","author":"Guo","year":"2018","journal-title":"Cell"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.15252\/embj.201694401","article-title":"The C9orf72 Protein Interacts with Rab1a and the ULK 1 Complex to Regulate Initiation of Autophagy","volume":"35","author":"Webster","year":"2016","journal-title":"EMBO J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/s41593-017-0047-3","article-title":"TDP-43 Pathology Disrupts Nuclear Pore Complexes and Nucleocytoplasmic Transport in ALS\/FTD","volume":"21","author":"Chou","year":"2018","journal-title":"Nat. Neurosci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nature14973","article-title":"The C9orf72 Repeat Expansion Disrupts Nucleocytoplasmic Transport","volume":"525","author":"Zhang","year":"2015","journal-title":"Nature"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/nature14974","article-title":"GGGGCC Repeat Expansion in C9orf72 Compromises Nucleocytoplasmic Transport","volume":"525","author":"Freibaum","year":"2015","journal-title":"Nature"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"eabe1923","DOI":"10.1126\/scitranslmed.abe1923","article-title":"Nuclear Accumulation of CHMP7 Initiates Nuclear Pore Complex Injury and Subsequent TDP-43 Dysfunction in Sporadic and Familial ALS","volume":"13","author":"Coyne","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1016\/j.neuron.2020.06.027","article-title":"G4C2 Repeat RNA Initiates a POM121-Mediated Reduction in Specific Nucleoporins in C9orf72 ALS\/FTD","volume":"107","author":"Coyne","year":"2020","journal-title":"Neuron"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/nn.4272","article-title":"C9ORF72 Poly(GA) Aggregates Sequester and Impair HR23 and Nucleocytoplasmic Transport Proteins","volume":"19","author":"Zhang","year":"2016","journal-title":"Nat. Neurosci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1038\/s41593-021-00859-9","article-title":"Interactions between ALS-Linked FUS and Nucleoporins Are Associated with Defects in the Nucleocytoplasmic Transport Pathway","volume":"24","author":"Lin","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1097\/00005072-199209000-00008","article-title":"Peripherin and Neurofilament Protein Coexist in Spinal Spheroids of Motor Neuron Disease","volume":"51","author":"Corbo","year":"1992","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/0304-3940(96)12314-4","article-title":"Ultrastructural Study of Synapses in the Anterior Horn Neurons of Patients with Amyotrophic Lateral Sclerosis","volume":"204","author":"Sasaki","year":"1996","journal-title":"Neurosci. Lett."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1002\/ana.410390119","article-title":"SOD1 Mutation Is Assosiated with Accumulation of Neurofilaments in Amyotrophic Lateral Scelaries","volume":"39","author":"Rouleau","year":"1996","journal-title":"Ann. Neurol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1097\/00005072-198409000-00001","article-title":"Fine Structural Observations of Neurofilamentous Changes in Amyotrophic Lateral Sclerosis","volume":"43","author":"Hirano","year":"1984","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"20523","DOI":"10.1073\/pnas.1006869107","article-title":"Deficits in Axonal Transport Precede ALS Symptoms in Vivo","volume":"107","author":"Bilsland","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1083\/jcb.200501085","article-title":"A Mutation in Dynein Rescues Axonal Transport Defects and Extends the Life Span of ALS Mice","volume":"169","author":"Kieran","year":"2005","journal-title":"J. Cell Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/4553","article-title":"Slowing of Axonal Transport Is a Very Early Event in the Toxicity of ALS\u2013Linked SOD1 Mutants to Motor Neurons","volume":"2","author":"Williamson","year":"1999","journal-title":"Nat. Neurosci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/S0006-8993(98)01351-1","article-title":"Selective Impairment of Fast Anterograde Axonal Transport in the Peripheral Nerves of Asymptomatic Transgenic Mice with a G93A Mutant SOD1 Gene","volume":"819","author":"Warita","year":"1999","journal-title":"Brain Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4706","DOI":"10.1093\/hmg\/ddt319","article-title":"The ALS Disease-Associated Mutant TDP-43 Impairs Mitochondrial Dynamics and Function in Motor Neurons","volume":"22","author":"Wang","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1093\/hmg\/ddt528","article-title":"Abnormal Mitochondrial Transport and Morphology Are Common Pathological Denominators in SOD1 and TDP43 ALS Mouse Models","volume":"23","author":"Cortez","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2720","DOI":"10.1093\/hmg\/ddm226","article-title":"Familial Amyotrophic Lateral Sclerosis-Linked SOD1 Mutants Perturb Fast Axonal Transport to Reduce Axonal Mitochondria Content","volume":"16","author":"Chapman","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.neuron.2013.12.018","article-title":"Axonal Transport of TDP-43 MRNA Granules Is Impaired by ALS-Causing Mutations","volume":"81","author":"Alami","year":"2014","journal-title":"Neuron"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1111\/gtc.12352","article-title":"TDP-43 Binds and Transports G-quadruplex-containing mRNAs into Neurites for Local Translation","volume":"21","author":"Ishiguro","year":"2016","journal-title":"Genes Cells"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3703","DOI":"10.1093\/hmg\/dds205","article-title":"The ALS Disease Protein TDP-43 Is Actively Transported in Motor Neuron Axons and Regulates Axon Outgrowth","volume":"21","author":"Fallini","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/j.neuron.2018.09.044","article-title":"ALS\/FTD-Linked Mutation in FUS Suppresses Intra-Axonal Protein Synthesis and Drives Disease Without Nuclear Loss-of-Function of FUS","volume":"100","author":"Tadokoro","year":"2018","journal-title":"Neuron"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.molcel.2012.09.025","article-title":"Physiological Roles of Mitochondrial Reactive Oxygen Species","volume":"48","author":"Sena","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1038\/nm.4130","article-title":"The Inhibition of TDP-43 Mitochondrial Localization Blocks Its Neuronal Toxicity","volume":"22","author":"Wang","year":"2016","journal-title":"Nat. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.15252\/embr.201541726","article-title":"ALS\/FTD-associated FUS Activates GSK-3\u03b2 to Disrupt the VAPB\u2013PTPIP51 Interaction and ER\u2013Mitochondria Associations","volume":"17","author":"Stoica","year":"2016","journal-title":"EMBO Rep."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3996","DOI":"10.1038\/ncomms4996","article-title":"ER\u2013Mitochondria Associations Are Regulated by the VAPB\u2013PTPIP51 Interaction and Are Disrupted by ALS\/FTD-Associated TDP-43","volume":"5","author":"Stoica","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"10851","DOI":"10.1523\/JNEUROSCI.1630-10.2010","article-title":"Wild-Type Human TDP-43 Expression Causes TDP-43 Phosphorylation, Mitochondrial Aggregation, Motor Deficits, and Early Mortality in Transgenic Mice","volume":"30","author":"Xu","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Peggion, C., Massimino, M.L., Bonadio, R.S., Lia, F., Lopreiato, R., Cagnin, S., Cal\u00ec, T., and Bertoli, A. (2021). Regulation of Endoplasmic Reticulum\u2013Mitochondria Tethering and Ca2+ Fluxes by TDP-43 via GSK3\u03b2. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111853"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.15252\/emmm.201606403","article-title":"Mitochondria-associated Membrane Collapse Is a Common Pathomechanism in SIGMAR1- and SOD1-linked ALS","volume":"8","author":"Watanabe","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.expneurol.2013.03.027","article-title":"Overexpression of Human Mutated G93A SOD1 Changes Dynamics of the ER Mitochondria Calcium Cycle Specifically in Mouse Embryonic Motor Neurons","volume":"247","author":"Prell","year":"2013","journal-title":"Exp. Neurol."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Kausar, S., Wang, F., and Cui, H. (2018). The Role of Mitochondria in Reactive Oxygen Species Generation and Its Implications for Neurodegenerative Diseases. Cells, 7.","DOI":"10.3390\/cells7120274"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/s41594-020-00537-7","article-title":"TDP-43 Aggregation Induced by Oxidative Stress Causes Global Mitochondrial Imbalance in ALS","volume":"28","author":"Zuo","year":"2021","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Arnold, F.J., Putka, A.F., Raychaudhuri, U., Hsu, S., Bedlack, R.S., Bennett, C.L., and La Spada, A.R. (2024). Revisiting Glutamate Excitotoxicity in Amyotrophic Lateral Sclerosis and Age-Related Neurodegeneration. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25115587"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1002\/1531-8249(199912)46:6<806::AID-ANA2>3.0.CO;2-S","article-title":"Reduction of GluR2 RNA Editing, a Molecular Change That Increases Calcium Influx through AMPA Receptors, Selective in the Spinal Ventral Gray of Patients with Amyotrophic Lateral Sclerosis","volume":"46","author":"Takuma","year":"1999","journal-title":"Ann. Neurol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"11917","DOI":"10.1523\/JNEUROSCI.2021-10.2010","article-title":"Induced Loss of ADAR2 Engenders Slow Death of Motor Neurons from Q\/R Site-Unedited GluR2","volume":"30","author":"Hideyama","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s00401-010-0678-x","article-title":"TDP-43 Pathology in Sporadic ALS Occurs in Motor Neurons Lacking the RNA Editing Enzyme ADAR2","volume":"120","author":"Aizawa","year":"2010","journal-title":"Acta Neuropathol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1001\/jamaneurol.2017.0357","article-title":"Characterization of Gene Expression Phenotype in Amyotrophic Lateral Sclerosis Monocytes","volume":"74","author":"Zhao","year":"2017","journal-title":"JAMA Neurol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S1474-4422(18)30394-6","article-title":"Immune Dysregulation in Amyotrophic Lateral Sclerosis: Mechanisms and Emerging Therapies","volume":"18","author":"Beers","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.neuron.2016.09.015","article-title":"Poly(GR) in C9ORF72 -Related ALS\/FTD Compromises Mitochondrial Function and Increases Oxidative Stress and DNA Damage in IPSC-Derived Motor Neurons","volume":"92","author":"Lu","year":"2016","journal-title":"Neuron"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1172\/JCI72723","article-title":"ALS-Associated Mutation FUS-R521C Causes DNA Damage and RNA Splicing Defects","volume":"124","author":"Qiu","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/s40478-024-01852-6","article-title":"ALS-Associated C21ORF2 Variant Disrupts DNA Damage Repair, Mitochondrial Metabolism, Neuronal Excitability and NEK1 Levels in Human Motor Neurons","volume":"12","author":"Zelina","year":"2024","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1007\/s00401-024-02688-z","article-title":"Neuronal STING Activation in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia","volume":"147","author":"Marques","year":"2024","journal-title":"Acta Neuropathol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/s41586-020-2625-x","article-title":"C9orf72 in Myeloid Cells Suppresses STING-Induced Inflammation","volume":"585","author":"McCauley","year":"2020","journal-title":"Nature"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/j.cell.2020.09.020","article-title":"TDP-43 Triggers Mitochondrial DNA Release via MPTP to Activate CGAS\/STING in ALS","volume":"183","author":"Yu","year":"2020","journal-title":"Cell"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"3753","DOI":"10.1038\/s41467-020-17514-9","article-title":"Knockout of Reactive Astrocyte Activating Factors Slows Disease Progression in an ALS Mouse Model","volume":"11","author":"Guttenplan","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1007\/s00439-016-1683-5","article-title":"The HnRNP Family: Insights into Their Role in Health and Disease","volume":"135","author":"Geuens","year":"2016","journal-title":"Hum. Genet."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1515\/hsz-2012-0115","article-title":"TDP-43 in Central Nervous System Development and Function: Clues to TDP-43-Associated Neurodegeneration","volume":"393","author":"Sephton","year":"2012","journal-title":"bchm"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"6826","DOI":"10.1074\/jbc.M109.061846","article-title":"TDP-43 Is a Developmentally Regulated Protein Essential for Early Embryonic Development","volume":"285","author":"Sephton","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1111\/febs.13651","article-title":"The TDP-43 N-terminal Domain Structure at High Resolution","volume":"283","author":"Romano","year":"2016","journal-title":"FEBS J."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"23928","DOI":"10.1038\/srep23928","article-title":"Two Mutations G335D and Q343R within the Amyloidogenic Core Region of TDP-43 Influence Its Aggregation and Inclusion Formation","volume":"6","author":"Jiang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"18619","DOI":"10.1073\/pnas.1413994112","article-title":"TDP-43 N Terminus Encodes a Novel Ubiquitin-like Fold and Its Unfolded Form in Equilibrium That Can Be Shifted by Binding to SsDNA","volume":"111","author":"Qin","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"4712","DOI":"10.1093\/nar\/gkt1407","article-title":"The Crystal Structure of TDP-43 RRM1-DNA Complex Reveals the Specific Recognition for UG- and TG-Rich Nucleic Acids","volume":"42","author":"Kuo","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1038\/nsmb.2698","article-title":"Molecular Basis of UG-Rich RNA Recognition by the Human Splicing Factor TDP-43","volume":"20","author":"Lukavsky","year":"2013","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.molmed.2011.06.004","article-title":"TDP-43 Functions and Pathogenic Mechanisms Implicated in TDP-43 Proteinopathies","volume":"17","author":"Cohen","year":"2011","journal-title":"Trends Mol. Med."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Fran\u00e7ois-Moutal, L., Perez-Miller, S., Scott, D.D., Miranda, V.G., Mollasalehi, N., and Khanna, M. (2019). Structural Insights Into TDP-43 and Effects of Post-Translational Modifications. Front. Mol. Neurosci., 12.","DOI":"10.3389\/fnmol.2019.00301"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"7083","DOI":"10.1038\/s41598-018-25008-4","article-title":"Active Nuclear Import and Passive Nuclear Export Are the Primary Determinants of TDP-43 Localization","volume":"8","author":"Pinarbasi","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"19614","DOI":"10.1074\/jbc.M113.463828","article-title":"Structural Transformation of the Amyloidogenic Core Region of TDP-43 Protein Initiates Its Aggregation and Cytoplasmic Inclusion","volume":"288","author":"Jiang","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/jhg.2012.24","article-title":"Novel TARDBP Mutations in Nordic ALS Patients","volume":"57","author":"Chiang","year":"2012","journal-title":"J. Hum. Genet."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"109166","DOI":"10.1016\/j.isci.2024.109166","article-title":"Homozygous ALS-Linked Mutations in TARDBP\/TDP-43 Lead to Hypoactivity and Synaptic Abnormalities in Human IPSC-Derived Motor Neurons","volume":"27","author":"Deneault","year":"2024","journal-title":"iScience"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Mejzini, R., Flynn, L.L., Pitout, I.L., Fletcher, S., Wilton, S.D., and Akkari, P.A. (2019). ALS Genetics, Mechanisms, and Therapeutics: Where Are We Now?. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.01310"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.ensci.2018.04.001","article-title":"TARDBP p.G376D Mutation, Found in Rapid Progressive Familial ALS, Induces Mislocalization of TDP-43","volume":"11","author":"Mitsuzawa","year":"2018","journal-title":"eNeurologicalSci"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/S1474-4422(08)70071-1","article-title":"TARDBP Mutations in Amyotrophic Lateral Sclerosis with TDP-43 Neuropathology: A Genetic and Histopathological Analysis","volume":"7","author":"Leverenz","year":"2008","journal-title":"Lancet Neurol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"3112","DOI":"10.1093\/hmg\/ddt166","article-title":"The Dual Functions of the Extreme N-Terminus of TDP-43 in Regulating Its Biological Activity and Inclusion Formation","volume":"22","author":"Zhang","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1007\/s10571-009-9489-9","article-title":"TDP-43 Dimerizes in Human Cells in Culture","volume":"30","author":"Shiina","year":"2010","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.bbrc.2012.07.071","article-title":"The N-Terminus of TDP-43 Promotes Its Oligomerization and Enhances DNA Binding Affinity","volume":"425","author":"Chang","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"12590","DOI":"10.1002\/anie.201706769","article-title":"The N-Terminal Domain of ALS-Linked TDP-43 Assembles without Misfolding","volume":"56","author":"Tsoi","year":"2017","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"13302","DOI":"10.1074\/jbc.M800342200","article-title":"Disturbance of Nuclear and Cytoplasmic TAR DNA-Binding Protein (TDP-43) Induces Disease-like Redistribution, Sequestration, and Aggregate Formation","volume":"283","author":"Winton","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1523\/JNEUROSCI.4988-09.2010","article-title":"Cytoplasmic Mislocalization of TDP-43 Is Toxic to Neurons and Enhanced by a Mutation Associated with Familial Amyotrophic Lateral Sclerosis","volume":"30","author":"Barmada","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"36337","DOI":"10.1074\/jbc.M104236200","article-title":"Characterization and Functional Implications of the RNA Binding Properties of Nuclear Factor TDP-43, a Novel Splicing Regulator OfCFTR Exon 9","volume":"276","author":"Buratti","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.jmb.2005.02.038","article-title":"Human, Drosophila, and C.Elegans TDP43: Nucleic Acid Binding Properties and Splicing Regulatory Function","volume":"348","author":"Ayala","year":"2005","journal-title":"J. Mol. Biol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1093\/nar\/gkp013","article-title":"Structural Insights into TDP-43 in Nucleic-Acid Binding and Domain Interactions","volume":"37","author":"Kuo","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1021\/acs.biochem.6b01088","article-title":"Phase to Phase with TDP-43","volume":"56","author":"Sun","year":"2017","journal-title":"Biochemistry"},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Huang, Y.-C., Lin, K.-F., He, R.-Y., Tu, P.-H., Koubek, J., Hsu, Y.-C., and Huang, J.J.-T. (2013). Inhibition of TDP-43 Aggregation by Nucleic Acid Binding. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0064002"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/emboj.2010.310","article-title":"TDP-43 Regulates Its MRNA Levels through a Negative Feedback Loop","volume":"30","author":"Ayala","year":"2011","journal-title":"EMBO J."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1534\/genetics.111.137760","article-title":"Prions in Yeast","volume":"191","author":"Liebman","year":"2012","journal-title":"Genetics"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.brainres.2012.01.016","article-title":"The Tip of the Iceberg: RNA-Binding Proteins with Prion-like Domains in Neurodegenerative Disease","volume":"1462","author":"King","year":"2012","journal-title":"Brain Res."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/ncb1843","article-title":"The Yeast Global Transcriptional Co-Repressor Protein Cyc8 Can Propagate as a Prion","volume":"11","author":"Patel","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1007\/s00018-016-2416-6","article-title":"Intrinsic Disorder in Proteins Involved in Amyotrophic Lateral Sclerosis","volume":"74","author":"Santamaria","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"4680","DOI":"10.1016\/j.cell.2021.07.018","article-title":"TDP-43 Condensation Properties Specify Its RNA-Binding and Regulatory Repertoire","volume":"184","author":"Hallegger","year":"2021","journal-title":"Cell"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"3778","DOI":"10.1242\/jcs.038950","article-title":"Structural Determinants of the Cellular Localization and Shuttling of TDP-43","volume":"121","author":"Ayala","year":"2008","journal-title":"J. Cell Sci."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.celrep.2017.09.028","article-title":"Post-Transcriptional Inhibition of Hsc70-4\/HSPA8 Expression Leads to Synaptic Vesicle Cycling Defects in Multiple Models of ALS","volume":"21","author":"Coyne","year":"2017","journal-title":"Cell Rep."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"5982","DOI":"10.1038\/s41598-023-33172-5","article-title":"ALS-Linked TDP-43 Mutations Interfere with the Recruitment of RNA Recognition Motifs to G-Quadruplex RNA","volume":"13","author":"Ishiguro","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"380","DOI":"10.2533\/chimia.2019.380","article-title":"Structural Transition, Function and Dysfunction of TDP-43 in Neurodegenerative Diseases","volume":"73","author":"Afroz","year":"2019","journal-title":"Chimia"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/nn.2778","article-title":"Characterizing the RNA Targets and Position-Dependent Splicing Regulation by TDP-43","volume":"14","author":"Tollervey","year":"2011","journal-title":"Nat. Neurosci."},{"key":"ref_152","first-page":"e111719","article-title":"Loss of TDP-43 Oligomerization or RNA Binding Elicits Distinct Aggregation Patterns","volume":"42","author":"Wiersma","year":"2023","journal-title":"EMBO J."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"e12925","DOI":"10.1111\/nan.12925","article-title":"Neuromuscular Junction Denervation and Terminal Schwann Cell Loss in the HTDP-43 Overexpression Mouse Model of Amyotrophic Lateral Sclerosis","volume":"49","author":"Alhindi","year":"2023","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Cappello, V., and Francolini, M. (2017). Neuromuscular Junction Dismantling in Amyotrophic Lateral Sclerosis. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18102092"},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Gelon, P.A., Dutchak, P.A., and Sephton, C.F. (2022). Synaptic Dysfunction in ALS and FTD: Anatomical and Molecular Changes Provide Insights into Mechanisms of Disease. Front. Mol. Neurosci., 15.","DOI":"10.3389\/fnmol.2022.1000183"},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Campanari, M.-L., Marian, A., Ciura, S., and Kabashi, E. (2021). TDP-43 Regulation of AChE Expression Can Mediate ALS-Like Phenotype in Zebrafish. Cells, 10.","DOI":"10.3390\/cells10020221"},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Strah, N., Romano, G., Introna, C., Klima, R., Marzullo, M., Ciapponi, L., Megighian, A., Nizzardo, M., and Feiguin, F. (2020). TDP-43 Promotes the Formation of Neuromuscular Synapses through the Regulation of Disc-Large Expression in Drosophila Skeletal Muscles. BMC Biol., 18.","DOI":"10.1186\/s12915-020-00767-7"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"6914","DOI":"10.1038\/s41467-021-27221-8","article-title":"Axonal TDP-43 Condensates Drive Neuromuscular Junction Disruption through Inhibition of Local Synthesis of Nuclear Encoded Mitochondrial Proteins","volume":"12","author":"Altman","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"16325","DOI":"10.1073\/pnas.1003459107","article-title":"Altered Distributions of Gemini of Coiled Bodies and Mitochondria in Motor Neurons of TDP-43 Transgenic Mice","volume":"107","author":"Shan","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"330","DOI":"10.7150\/thno.51004","article-title":"TDP-43 Proteinopathy Impairs MRNP Granule Mediated Postsynaptic Translation and MRNA Metabolism","volume":"11","author":"Wong","year":"2021","journal-title":"Theranostics"},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Huang, W., Zhou, Y., Tu, L., Ba, Z., Huang, J., Huang, N., and Luo, Y. (2020). TDP-43: From Alzheimer\u2019s Disease to Limbic-Predominant Age-Related TDP-43 Encephalopathy. Front. Mol. Neurosci., 13.","DOI":"10.3389\/fnmol.2020.00026"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"2983","DOI":"10.1093\/brain\/aww224","article-title":"TDP-43 Stage, Mixed Pathologies, and Clinical Alzheimer\u2019s-Type Dementia","volume":"139","author":"James","year":"2016","journal-title":"Brain"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"105130","DOI":"10.1016\/j.nbd.2020.105130","article-title":"TDP-43 and Tau Oligomers in Alzheimer\u2019s Disease, Amyotrophic Lateral Sclerosis, and Frontotemporal Dementia","volume":"146","author":"Montalbano","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1093\/brain\/awz099","article-title":"Limbic-Predominant Age-Related TDP-43 Encephalopathy (LATE): Consensus Working Group Report","volume":"142","author":"Nelson","year":"2019","journal-title":"Brain"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1038\/s41580-020-00326-6","article-title":"Biomolecular Condensates at the Nexus of Cellular Stress, Protein Aggregation Disease and Ageing","volume":"22","author":"Alberti","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1146\/annurev-genet-112618-043527","article-title":"Liquid-Liquid Phase Separation in Disease","volume":"53","author":"Alberti","year":"2019","journal-title":"Annu. Rev. Genet."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1016\/j.cell.2018.10.042","article-title":"Transcription Factors Activate Genes through the Phase-Separation Capacity of Their Activation Domains","volume":"175","author":"Boija","year":"2018","journal-title":"Cell"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.cell.2017.02.007","article-title":"A Phase Separation Model for Transcriptional Control","volume":"169","author":"Hnisz","year":"2017","journal-title":"Cell"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/s41556-020-0485-0","article-title":"Phase Separation of TAZ Compartmentalizes the Transcription Machinery to Promote Gene Expression","volume":"22","author":"Lu","year":"2020","journal-title":"Nat. Cell Biol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/s41580-020-00303-z","article-title":"A Framework for Understanding the Functions of Biomolecular Condensates across Scales","volume":"22","author":"Lyon","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/j.molcel.2022.02.005","article-title":"Receptor Tyrosine Kinases Regulate Signal Transduction through a Liquid-Liquid Phase Separated State","volume":"82","author":"Lin","year":"2022","journal-title":"Mol. Cell"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nrm.2017.7","article-title":"Biomolecular Condensates: Organizers of Cellular Biochemistry","volume":"18","author":"Banani","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"e04123","DOI":"10.7554\/eLife.04123","article-title":"Phase Transitions of Multivalent Proteins Can Promote Clustering of Membrane Receptors","volume":"3","author":"Banjade","year":"2014","journal-title":"eLife"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1146\/annurev-cellbio-100913-013325","article-title":"Liquid-Liquid Phase Separation in Biology","volume":"30","author":"Hyman","year":"2014","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.tcb.2018.02.004","article-title":"Protein Phase Separation: A New Phase in Cell Biology","volume":"28","author":"Boeynaems","year":"2018","journal-title":"Trends Cell Biol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1016\/j.celrep.2018.01.036","article-title":"Intrinsically Disordered Regions Can Contribute Promiscuous Interactions to RNP Granule Assembly","volume":"22","author":"Protter","year":"2018","journal-title":"Cell Rep."},{"key":"ref_177","first-page":"694","article-title":"Valence and Patterning of Aromatic Residues Determine the Phase Behavior of Prion-like Domains","volume":"367","author":"Martin","year":"2020","journal-title":"Science (1979)"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.cell.2016.06.010","article-title":"Compositional Control of Phase-Separated Cellular Bodies","volume":"166","author":"Banani","year":"2016","journal-title":"Cell"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"7137","DOI":"10.1074\/jbc.TM118.001189","article-title":"Friend or Foe-Post-Translational Modifications as Regulators of Phase Separation and RNP Granule Dynamics","volume":"294","author":"Hofweber","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.cell.2015.09.015","article-title":"Phase Separation by Low Complexity Domains Promotes Stress Granule Assembly and Drives Pathological Fibrillization","volume":"163","author":"Molliex","year":"2015","journal-title":"Cell"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"6090","DOI":"10.1074\/jbc.AC117.001037","article-title":"TAR DNA-Binding Protein 43 (TDP-43) Liquid\u2013Liquid Phase Separation Is Mediated by Just a Few Aromatic Residues","volume":"293","author":"Li","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Gao, J., Wang, L., Ren, X., Dunn, J.R., Peters, A., Miyagi, M., Fujioka, H., Zhao, F., Askwith, C., and Liang, J. (2021). Translational Regulation in the Brain by TDP-43 Phase Separation. J. Cell Biol., 220.","DOI":"10.1083\/jcb.202101019"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1039\/D1SC05672G","article-title":"Determinants for Intrinsically Disordered Protein Recruitment into Phase-Separated Protein Condensates","volume":"13","author":"Jo","year":"2022","journal-title":"Chem. Sci."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.tibs.2020.05.002","article-title":"Mechanisms and Regulation of RNA Condensation in RNP Granule Formation","volume":"45","author":"Tauber","year":"2020","journal-title":"Trends Biochem. Sci."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"5035","DOI":"10.1021\/acs.jpcb.1c02286","article-title":"Effect of RNA on Morphology and Dynamics of Membraneless Organelles","volume":"125","author":"Ranganathan","year":"2021","journal-title":"J. Phys. Chem. B"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"7115","DOI":"10.1074\/jbc.TM118.001192","article-title":"The Molecular Language of Membraneless Organelles","volume":"294","author":"Gomes","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.cell.2020.03.050","article-title":"Competing Protein-RNA Interaction Networks Control Multiphase Intracellular Organization","volume":"181","author":"Sanders","year":"2020","journal-title":"Cell"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.cell.2020.03.049","article-title":"RNA-Induced Conformational Switching and Clustering of G3BP Drive Stress Granule Assembly by Condensation","volume":"181","author":"Kopach","year":"2020","journal-title":"Cell"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"e53632","DOI":"10.15252\/embr.202153632","article-title":"Specific RNA Interactions Promote TDP-43 Multivalent Phase Separation and Maintain Liquid Properties","volume":"22","author":"Grese","year":"2021","journal-title":"EMBO Rep."},{"key":"ref_190","doi-asserted-by":"crossref","unstructured":"Alberti, S., Mateju, D., Mediani, L., and Carra, S. (2017). Granulostasis: Protein Quality Control of RNP Granules. Front. Mol. Neurosci., 10.","DOI":"10.3389\/fnmol.2017.00084"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.tibs.2007.12.003","article-title":"Stress Granules: The Tao of RNA Triage","volume":"33","author":"Anderson","year":"2008","journal-title":"Trends Biochem. Sci."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.cell.2012.04.017","article-title":"Cell-Free Formation of RNA Granules: Low Complexity Sequence Domains Form Dynamic Fibers within Hydrogels","volume":"149","author":"Kato","year":"2012","journal-title":"Cell"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1016\/j.molcel.2015.01.013","article-title":"Phase Transition of a Disordered Nuage Protein Generates Environmentally Responsive Membraneless Organelles","volume":"57","author":"Nott","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/j.molcel.2017.02.013","article-title":"Phase Separation of C9orf72 Dipeptide Repeats Perturbs Stress Granule Dynamics","volume":"65","author":"Boeynaems","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_195","doi-asserted-by":"crossref","unstructured":"Chien, H.-M., Lee, C.-C., and Huang, J.J.-T. (2021). The Different Faces of the TDP-43 Low-Complexity Domain: The Formation of Liquid Droplets and Amyloid Fibrils. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22158213"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/s41594-018-0064-2","article-title":"Atomic Structures of TDP-43 LCD Segments and Insights into Reversible or Pathogenic Aggregation","volume":"25","author":"Guenther","year":"2018","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1016\/j.celrep.2016.06.088","article-title":"In Vivo Formation of Vacuolated Multi-Phase Compartments Lacking Membranes","volume":"16","author":"Schmidt","year":"2016","journal-title":"Cell Rep."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"3353","DOI":"10.1093\/hmg\/ddp275","article-title":"Truncation and Pathogenic Mutations Facilitate the Formation of Intracellular Aggregates of TDP-43","volume":"18","author":"Nonaka","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1038\/nsmb.2053","article-title":"An ALS-Associated Mutation Affecting TDP-43 Enhances Protein Aggregation, Fibril Formation and Neurotoxicity","volume":"18","author":"Guo","year":"2011","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_200","doi-asserted-by":"crossref","unstructured":"Sun, C.-S., Wang, C.Y.-H., Chen, B.P.-W., He, R.-Y., Liu, G.C.-H., Wang, C.-H., Chen, W., Chern, Y., and Huang, J.J.-T. (2014). The Influence of Pathological Mutations and Proline Substitutions in TDP-43 Glycine-Rich Peptides on Its Amyloid Properties and Cellular Toxicity. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0103644"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/sj.emboj.7601930","article-title":"The Two Faces of Protein Misfolding: Gain- and Loss-of-Function in Neurodegenerative Diseases","volume":"27","author":"Winklhofer","year":"2008","journal-title":"EMBO J."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"5550","DOI":"10.1038\/s41467-022-32940-7","article-title":"Protein Condensation Diseases: Therapeutic Opportunities","volume":"13","author":"Vendruscolo","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1146\/annurev.biochem.75.101304.123901","article-title":"Protein Misfolding, Functional Amyloid, and Human Disease","volume":"75","author":"Chiti","year":"2006","journal-title":"Annu. Rev. Biochem."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1038\/nature02261","article-title":"Protein Folding and Misfolding","volume":"426","author":"Dobson","year":"2003","journal-title":"Nature"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"a033878","DOI":"10.1101\/cshperspect.a033878","article-title":"The Amyloid Phenomenon and Its Significance in Biology and Medicine","volume":"12","author":"Dobson","year":"2020","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/nature10317","article-title":"Molecular Chaperones in Protein Folding and Proteostasis","volume":"475","author":"Hartl","year":"2011","journal-title":"Nature"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nsmb.3380","article-title":"Mechanistic Basis for the Recognition of a Misfolded Protein by the Molecular Chaperone Hsp90","volume":"24","author":"Oroz","year":"2017","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"783","DOI":"10.15252\/embj.201593378","article-title":"Hsp70 Displaces Small Heat Shock Proteins from Aggregates to Initiate Protein Refolding","volume":"36","author":"Obuchowski","year":"2017","journal-title":"EMBO J."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"13673","DOI":"10.1038\/ncomms13673","article-title":"Small Heat Shock Proteins Sequester Misfolding Proteins in Near-Native Conformation for Cellular Protection and Efficient Refolding","volume":"7","author":"Ungelenk","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"21399","DOI":"10.1074\/jbc.M113.479253","article-title":"Hsp110 Is a Bona Fide Chaperone Using ATP to Unfold Stable Misfolded Polypeptides and Reciprocally Collaborate with Hsp70 to Solubilize Protein Aggregates","volume":"288","author":"Mattoo","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.molcel.2018.01.004","article-title":"Cellular Handling of Protein Aggregates by Disaggregation Machines","volume":"69","author":"Mogk","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_212","doi-asserted-by":"crossref","unstructured":"Shorter, J. (2011). The Mammalian Disaggregase Machinery: Hsp110 Synergizes with Hsp70 and Hsp40 to Catalyze Protein Disaggregation and Reactivation in a Cell-Free System. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026319"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"168615","DOI":"10.1016\/j.jmb.2024.168615","article-title":"Interplay of Proteostasis Capacity and Protein Aggregation: Implications for Cellular Function and Disease","volume":"436","author":"Hipp","year":"2024","journal-title":"J. Mol. Biol."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1038\/nsmb.1591","article-title":"Converging Concepts of Protein Folding in Vitro and in Vivo","volume":"16","author":"Hartl","year":"2009","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"3761","DOI":"10.1021\/jp412819j","article-title":"Minimal Model of Self-Assembly: Emergence of Diversity and Complexity","volume":"118","author":"Barz","year":"2014","journal-title":"J. Phys. Chem. B"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1002\/pro.2524","article-title":"A Brief Overview of Amyloids and Alzheimer\u2019s Disease","volume":"23","author":"Ow","year":"2014","journal-title":"Protein Sci."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.nbd.2012.03.005","article-title":"Naphthoquinone-Tyrptophan Reduces Neurotoxic A\u03b2*56 Levels and Improves Cognition in Alzheimer\u2019s Disease Animal Model","volume":"46","author":"Farfara","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1016\/j.bpj.2011.02.060","article-title":"Systematic Examination of Polymorphism in Amyloid Fibrils by Molecular-Dynamics Simulation","volume":"100","author":"Berryman","year":"2011","journal-title":"Biophys. J."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1002\/jps.23354","article-title":"Application of Second-Derivative Fluorescence Spectroscopy to Monitor Subtle Changes in a Monoclonal Antibody Structure","volume":"102","author":"Abbas","year":"2013","journal-title":"J. Pharm. Sci."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1021\/mp2004109","article-title":"Mapping Site-Specific Changes That Affect Stability of the N-Terminal Domain of Calmodulin","volume":"9","author":"Krause","year":"2012","journal-title":"Mol. Pharm."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"2595","DOI":"10.1016\/j.bpj.2012.03.057","article-title":"Characterizing Intermolecular Interactions That Initiate Native-Like Protein Aggregation","volume":"102","author":"Bemporad","year":"2012","journal-title":"Biophys. J."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1016\/j.sbi.2008.10.002","article-title":"Function and Structure of Inherently Disordered Proteins","volume":"18","author":"Dunker","year":"2008","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/j.celrep.2013.09.043","article-title":"Widespread Aggregation and Neurodegenerative Diseases Are Associated with Supersaturated Proteins","volume":"5","author":"Ciryam","year":"2013","journal-title":"Cell Rep."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.tcb.2014.05.003","article-title":"Proteostasis Impairment in Protein-Misfolding and -Aggregation Diseases","volume":"24","author":"Hipp","year":"2014","journal-title":"Trends Cell Biol."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.ijbiomac.2017.05.048","article-title":"Protein Aggregation: From Background to Inhibition Strategies","volume":"103","author":"Alam","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_226","doi-asserted-by":"crossref","unstructured":"Vivoli-Vega, M., Guri, P., Chiti, F., and Bemporad, F. (2020). Insight into the Folding and Dimerization Mechanisms of the N-Terminal Domain from Human TDP-43. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176259"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"8264","DOI":"10.1074\/jbc.M113.542779","article-title":"Folding of the RNA Recognition Motif (RRM) Domains of the Amyotrophic Lateral Sclerosis (ALS)-Linked Protein TDP-43 Reveals an Intermediate State","volume":"289","author":"Mackness","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"6696","DOI":"10.1074\/jbc.RA118.005889","article-title":"Detection of TAR DNA-Binding Protein 43 (TDP-43) Oligomers as Initial Intermediate Species during Aggregate Formation","volume":"294","author":"French","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.molcel.2015.08.018","article-title":"Formation and Maturation of Phase-Separated Liquid Droplets by RNA-Binding Proteins","volume":"60","author":"Lin","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.molcel.2015.09.006","article-title":"Residue-by-Residue View of In Vitro FUS Granules That Bind the C-Terminal Domain of RNA Polymerase II","volume":"60","author":"Burke","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1002\/1873-3468.12698","article-title":"Perfecting Prediction of Mutational Impact on the Aggregation Propensity of the ALS-associated HnRNPA2 Prion-like Protein","volume":"591","author":"Batlle","year":"2017","journal-title":"FEBS Lett."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.cell.2013.07.038","article-title":"Altered Ribostasis: RNA-Protein Granules in Degenerative Disorders","volume":"154","author":"Ramaswami","year":"2013","journal-title":"Cell"},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"eaaf4382","DOI":"10.1126\/science.aaf4382","article-title":"Liquid Phase Condensation in Cell Physiology and Disease","volume":"357","author":"Shin","year":"2017","journal-title":"Science"},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1083\/jcb.201302044","article-title":"Stress Granules as Crucibles of ALS Pathogenesis","volume":"201","author":"Li","year":"2013","journal-title":"J. Cell Biol."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1016\/j.cell.2016.04.047","article-title":"Coexisting Liquid Phases Underlie Nucleolar Subcompartments","volume":"165","author":"Feric","year":"2016","journal-title":"Cell"},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.neuron.2015.10.030","article-title":"ALS\/FTD Mutation-Induced Phase Transition of FUS Liquid Droplets and Reversible Hydrogels into Irreversible Hydrogels Impairs RNP Granule Function","volume":"88","author":"Murakami","year":"2015","journal-title":"Neuron"},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1126\/science.277.5334.1975","article-title":"Enhancement of Protein Crystal Nucleation by Critical Density Fluctuations","volume":"277","author":"Frenkel","year":"1997","journal-title":"Science"},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1016\/j.jmb.2020.03.004","article-title":"Liquid\u2013Liquid Phase Separation and Its Mechanistic Role in Pathological Protein Aggregation","volume":"432","author":"Babinchak","year":"2020","journal-title":"J. Mol. Biol."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.neuron.2017.07.025","article-title":"TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics","volume":"95","author":"Mackenzie","year":"2017","journal-title":"Neuron"},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.cell.2018.03.056","article-title":"FUS Phase Separation Is Modulated by a Molecular Chaperone and Methylation of Arginine Cation-\u03c0 Interactions","volume":"173","author":"Qamar","year":"2018","journal-title":"Cell"},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.adgen.2015.07.001","article-title":"Functional Significance of TDP-43 Mutations in Disease","volume":"91","author":"Buratti","year":"2015","journal-title":"Adv. Genet."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"23281","DOI":"10.1038\/srep23281","article-title":"Mass Spectrometric Analysis of Accumulated TDP-43 in Amyotrophic Lateral Sclerosis Brains","volume":"6","author":"Kametani","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1002\/ana.21425","article-title":"Phosphorylated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis","volume":"64","author":"Hasegawa","year":"2008","journal-title":"Ann. Neurol."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1038\/nphys3532","article-title":"Polymer Physics of Intracellular Phase Transitions","volume":"11","author":"Brangwynne","year":"2015","journal-title":"Nat. Phys."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1093\/hmg\/ddt498","article-title":"TDP-43 Phosphorylation by Casein Kinase I\u03b5 Promotes Oligomerization and Enhances Toxicity in Vivo","volume":"23","author":"Choksi","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1002\/ana.23870","article-title":"CDC7 Inhibition Blocks Pathological TDP-43 Phosphorylation and Neurodegeneration","volume":"74","author":"Liachko","year":"2013","journal-title":"Ann. Neurol."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s00401-008-0477-9","article-title":"Phosphorylation of S409\/410 of TDP-43 Is a Consistent Feature in All Sporadic and Familial Forms of TDP-43 Proteinopathies","volume":"117","author":"Neumann","year":"2009","journal-title":"Acta Neuropathol."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"5473","DOI":"10.1074\/jbc.M115.695379","article-title":"Phosphorylation of TAR DNA-Binding Protein of 43 KDa (TDP-43) by Truncated Casein Kinase 1\u03b4 Triggers Mislocalization and Accumulation of TDP-43","volume":"291","author":"Nonaka","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_249","first-page":"e108443","article-title":"Disease-Linked TDP-43 Hyperphosphorylation Suppresses TDP-43 Condensation and Aggregation","volume":"41","author":"Simonetti","year":"2022","journal-title":"EMBO J."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.15252\/embj.201695957","article-title":"An Aberrant Phase Transition of Stress Granules Triggered by Misfolded Protein and Prevented by Chaperone Function","volume":"36","author":"Mateju","year":"2017","journal-title":"EMBO J."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1007\/s12192-020-01141-w","article-title":"BAG3 and BAG6 Differentially Affect the Dynamics of Stress Granules by Targeting Distinct Subsets of Defective Polypeptides Released from Ribosomes","volume":"25","author":"Mediani","year":"2020","journal-title":"Cell Stress Chaperones"},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.molcel.2019.09.016","article-title":"The Control Centers of Biomolecular Phase Separation: How Membrane Surfaces, PTMs, and Active Processes Regulate Condensation","volume":"76","author":"Snead","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1093\/emboj\/16.3.659","article-title":"A Small Heat Shock Protein Stably Binds Heat-Denatured Model Substrates and Can Maintain a Substrate in a Folding-Competent State","volume":"16","author":"Lee","year":"1997","journal-title":"EMBO J."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1006\/bbrc.1994.2586","article-title":"Cells Overexpressing Hsp27 Show Accelerated Recovery from Heat-Induced Nuclear-Protein Aggregation","volume":"204","author":"Kampinga","year":"1994","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1093\/emboj\/16.2.221","article-title":"Binding of Non-Native Protein to Hsp25 during Heat Shock Creates a Reservoir of Folding Intermediates for Reactivation","volume":"16","author":"Ehrnsperger","year":"1997","journal-title":"EMBO J."},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.molcel.2022.01.005","article-title":"Chaperones Directly and Efficiently Disperse Stress-Triggered Biomolecular Condensates","volume":"82","author":"Yoo","year":"2022","journal-title":"Mol. Cell"},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"23869","DOI":"10.1074\/jbc.M502854200","article-title":"A Chaperone Pathway in Protein Disaggregation","volume":"280","author":"Cashikar","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.molcel.2019.03.019","article-title":"C9orf72 Poly(PR) Dipeptide Repeats Disturb Biomolecular Phase Separation and Disrupt Nucleolar Function","volume":"74","author":"White","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"e42315","DOI":"10.7554\/eLife.42315","article-title":"Spatial Control of Irreversible Protein Aggregation","volume":"8","author":"Weber","year":"2019","journal-title":"eLife"},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.molcel.2016.07.021","article-title":"A Surveillance Function of the HSPB8-BAG3-HSP70 Chaperone Complex Ensures Stress Granule Integrity and Dynamism","volume":"63","author":"Ganassi","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"e101341","DOI":"10.15252\/embj.2018101341","article-title":"Defective Ribosomal Products Challenge Nuclear Function by Impairing Nuclear Condensate Dynamics and Immobilizing Ubiquitin","volume":"38","author":"Mediani","year":"2019","journal-title":"EMBO J."},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"e51740","DOI":"10.15252\/embr.202051740","article-title":"Hsp90-mediated Regulation of DYRK3 Couples Stress Granule Disassembly and Growth via MTORC1 Signaling","volume":"22","author":"Mediani","year":"2021","journal-title":"EMBO Rep."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1083\/jcb.201709072","article-title":"Pathways of Cellular Proteostasis in Aging and Disease","volume":"217","author":"Klaips","year":"2018","journal-title":"J. Cell Biol."},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"a004374","DOI":"10.1101\/cshperspect.a004374","article-title":"Cellular Strategies of Protein Quality Control","volume":"3","author":"Chen","year":"2011","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"4464","DOI":"10.1111\/febs.15617","article-title":"Alternative Systems for Misfolded Protein Clearance: Life beyond the Proteasome","volume":"288","author":"Johnston","year":"2021","journal-title":"FEBS J."},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1038\/ncb2838","article-title":"Spatial Sequestration of Misfolded Proteins by a Dynamic Chaperone Pathway Enhances Cellular Fitness during Stress","volume":"15","author":"Vonk","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"ref_267","doi-asserted-by":"crossref","unstructured":"Naskar, A., Nayak, A., Salaikumaran, M.R., Vishal, S.S., and Gopal, P.P. (2023). Phase Separation and Pathologic Transitions of RNP Condensates in Neurons: Implications for Amyotrophic Lateral Sclerosis, Frontotemporal Dementia and Other Neurodegenerative Disorders. Front. Mol. Neurosci., 16.","DOI":"10.3389\/fnmol.2023.1242925"},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"12125","DOI":"10.1038\/ncomms12125","article-title":"NEDDylation Promotes Stress Granule Assembly","volume":"7","author":"Jayabalan","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.tcb.2016.05.004","article-title":"Principles and Properties of Stress Granules","volume":"26","author":"Protter","year":"2016","journal-title":"Trends Cell Biol."},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.cell.2013.07.031","article-title":"Inhibition of MTORC1 by Astrin and Stress Granules Prevents Apoptosis in Cancer Cells","volume":"154","author":"Thedieck","year":"2013","journal-title":"Cell"},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.cell.2020.03.046","article-title":"G3BP1 Is a Tunable Switch That Triggers Phase Separation to Assemble Stress Granules","volume":"181","author":"Yang","year":"2020","journal-title":"Cell"},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.cell.2015.12.038","article-title":"ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure","volume":"164","author":"Jain","year":"2016","journal-title":"Cell"},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.cell.2017.12.032","article-title":"Context-Dependent and Disease-Specific Diversity in Protein Interactions within Stress Granules","volume":"172","author":"Markmiller","year":"2018","journal-title":"Cell"},{"key":"ref_274","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.molcel.2020.10.032","article-title":"Spatiotemporal Proteomic Analysis of Stress Granule Disassembly Using APEX Reveals Regulation by SUMOylation and Links to ALS Pathogenesis","volume":"80","author":"Siany","year":"2020","journal-title":"Mol. Cell"},{"key":"ref_275","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.molcel.2017.12.020","article-title":"High-Density Proximity Mapping Reveals the Subcellular Organization of MRNA-Associated Granules and Bodies","volume":"69","author":"Youn","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1016\/j.jmb.2020.02.020","article-title":"Distinct Features of Stress Granule Proteins Predict Localization in Membraneless Organelles","volume":"432","author":"Kuechler","year":"2020","journal-title":"J. Mol. Biol."},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1038\/35008096","article-title":"Rapid Degradation of a Large Fraction of Newly Synthesized Proteins by Proteasomes","volume":"404","author":"Schubert","year":"2000","journal-title":"Nature"},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"107230","DOI":"10.1016\/j.jbc.2024.107230","article-title":"Structural Insight into the ZFAND1\u2013P97 Interaction Involved in Stress Granule Clearance","volume":"300","author":"Lai","year":"2024","journal-title":"J. Biol. Chem."},{"key":"ref_279","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/j.molcel.2018.04.021","article-title":"ZFAND1 Recruits P97 and the 26S Proteasome to Promote the Clearance of Arsenite-Induced Stress Granules","volume":"70","author":"Turakhiya","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_280","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1038\/cdd.2014.103","article-title":"Inhibition of Autophagy, Lysosome and VCP Function Impairs Stress Granule Assembly","volume":"21","author":"Seguin","year":"2014","journal-title":"Cell Death Differ."},{"key":"ref_281","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.molcel.2020.05.017","article-title":"The Nuclear SUMO-Targeted Ubiquitin Quality Control Network Regulates the Dynamics of Cytoplasmic Stress Granules","volume":"79","author":"Wagner","year":"2020","journal-title":"Mol. Cell"},{"key":"ref_282","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/s41589-021-00801-x","article-title":"Mechanistic Dissection of Increased Enzymatic Rate in a Phase-Separated Compartment","volume":"17","author":"Peeples","year":"2021","journal-title":"Nat. Chem. Biol."},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"166624","DOI":"10.1016\/j.jmb.2020.08.009","article-title":"Enzymatic Reactions inside Biological Condensates","volume":"433","author":"Zhang","year":"2021","journal-title":"J. Mol. Biol."},{"key":"ref_284","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.neuron.2019.01.048","article-title":"RNA Binding Antagonizes Neurotoxic Phase Transitions of TDP-43","volume":"102","author":"Mann","year":"2019","journal-title":"Neuron"},{"key":"ref_285","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.molcel.2018.07.002","article-title":"Poly(ADP-Ribose) Prevents Pathological Phase Separation of TDP-43 by Promoting Liquid Demixing and Stress Granule Localization","volume":"71","author":"McGurk","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_286","doi-asserted-by":"crossref","first-page":"eadq2475","DOI":"10.1126\/sciadv.adq2475","article-title":"SUMO2\/3 Conjugation of TDP-43 Protects against Aggregation","volume":"11","author":"Verde","year":"2025","journal-title":"Sci. Adv."},{"key":"ref_287","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1111\/j.1471-4159.2009.06383.x","article-title":"TDP-43 Is Recruited to Stress Granules in Conditions of Oxidative Insult","volume":"111","author":"Colombrita","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_288","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/s41583-019-0222-5","article-title":"Stress Granules and Neurodegeneration","volume":"20","author":"Wolozin","year":"2019","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_289","doi-asserted-by":"crossref","first-page":"101336","DOI":"10.1016\/j.arr.2021.101336","article-title":"Post-Translational Modifications: Regulators of Neurodegenerative Proteinopathies","volume":"68","author":"Gupta","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_290","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/nature10879","article-title":"Phase Transitions in the Assembly of Multivalent Signalling Proteins","volume":"483","author":"Li","year":"2012","journal-title":"Nature"},{"key":"ref_291","doi-asserted-by":"crossref","first-page":"5404","DOI":"10.1074\/jbc.TM117.000117","article-title":"Ubiquitin Signaling and Autophagy","volume":"293","author":"Grumati","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_292","doi-asserted-by":"crossref","first-page":"eabf6548","DOI":"10.1126\/science.abf6548","article-title":"Ubiquitination of G3BP1 Mediates Stress Granule Disassembly in a Context-Specific Manner","volume":"372","author":"Gwon","year":"2021","journal-title":"Science"},{"key":"ref_293","doi-asserted-by":"crossref","first-page":"194989","DOI":"10.1016\/j.bbagrm.2023.194989","article-title":"Post-Translational Modifications in Stress Granule and Their Implications in Neurodegenerative Diseases","volume":"1866","author":"Wang","year":"2023","journal-title":"Biochim. Et Biophys. Acta (BBA)-Gene Regul. Mech."},{"key":"ref_294","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1080\/15548627.2022.2164427","article-title":"Stress Granule Homeostasis Is Modulated by TRIM21-Mediated Ubiquitination of G3BP1 and Autophagy-Dependent Elimination of Stress Granules","volume":"19","author":"Yang","year":"2023","journal-title":"Autophagy"},{"key":"ref_295","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1126\/science.1134108","article-title":"Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis","volume":"314","author":"Neumann","year":"2006","journal-title":"Science"},{"key":"ref_296","doi-asserted-by":"crossref","first-page":"5682","DOI":"10.1007\/s12035-021-02505-8","article-title":"SUMOylation Regulates TDP-43 Splicing Activity and Nucleocytoplasmic Distribution","volume":"58","author":"Maraschi","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_297","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1007\/s12035-019-01810-7","article-title":"A Role for SUMOylation in the Formation and Cellular Localization of TDP-43 Aggregates in Amyotrophic Lateral Sclerosis","volume":"57","author":"Maurel","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_298","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1038\/emboj.2011.471","article-title":"Redox Signalling Directly Regulates TDP-43 via Cysteine Oxidation and Disulphide Cross-Linking","volume":"31","author":"Cohen","year":"2012","journal-title":"EMBO J."},{"key":"ref_299","doi-asserted-by":"crossref","first-page":"115205","DOI":"10.1016\/j.celrep.2024.115205","article-title":"Opposing Roles of P38\u03b1-Mediated Phosphorylation and PRMT1-Mediated Arginine Methylation in Driving TDP-43 Proteinopathy","volume":"44","author":"Aikio","year":"2025","journal-title":"Cell Rep."},{"key":"ref_300","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1038\/s41586-023-06405-w","article-title":"TDP-43 Forms Amyloid Filaments with a Distinct Fold in Type A FTLD-TDP","volume":"620","author":"Arseni","year":"2023","journal-title":"Nature"},{"key":"ref_301","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1159\/000287952","article-title":"Caspase-Cleaved Transactivation Response DNA-Binding Protein 43 in Parkinson\u2019s Disease and Dementia with Lewy Bodies","volume":"7","author":"Kokoulina","year":"2010","journal-title":"Neurodegener. Dis."},{"key":"ref_302","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1016\/j.febslet.2015.06.009","article-title":"TDP-35 Sequesters TDP-43 into Cytoplasmic Inclusions through Binding with RNA","volume":"589","author":"Che","year":"2015","journal-title":"FEBS Lett."},{"key":"ref_303","doi-asserted-by":"crossref","first-page":"7289","DOI":"10.1038\/ncomms8289","article-title":"System-Wide Identification of Wild-Type SUMO-2 Conjugation Sites","volume":"6","author":"Hendriks","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_304","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nsmb.3366","article-title":"Site-Specific Mapping of the Human SUMO Proteome Reveals Co-Modification with Phosphorylation","volume":"24","author":"Hendriks","year":"2017","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_305","doi-asserted-by":"crossref","unstructured":"van Eersel, J., Ke, Y.D., Gladbach, A., Bi, M., G\u00f6tz, J., Kril, J.J., and Ittner, L.M. (2011). Cytoplasmic Accumulation and Aggregation of TDP-43 upon Proteasome Inhibition in Cultured Neurons. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0022850"},{"key":"ref_306","first-page":"1263","article-title":"Differential Roles of the Ubiquitin Proteasome System and Autophagy in the Clearance of Soluble and Aggregated TDP-43 Species","volume":"127","author":"Scotter","year":"2014","journal-title":"J. Cell Sci."},{"key":"ref_307","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.bbrc.2006.10.093","article-title":"TDP-43 Is a Component of Ubiquitin-Positive Tau-Negative Inclusions in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis","volume":"351","author":"Arai","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_308","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1007\/s11357-021-00383-5","article-title":"Regulation of TDP-43 Phosphorylation in Aging and Disease","volume":"43","author":"Eck","year":"2021","journal-title":"Geroscience"},{"key":"ref_309","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1750-1326-5-33","article-title":"Phosphorylation Regulates Proteasomal-Mediated Degradation and Solubility of TAR DNA Binding Protein-43 C-Terminal Fragments","volume":"5","author":"Zhang","year":"2010","journal-title":"Mol. Neurodegener."},{"key":"ref_310","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.bpj.2024.01.001","article-title":"Phosphomimetic Substitutions in TDP-43\u2019s Transiently \u03b1-Helical Region Suppress Phase Separation","volume":"123","author":"Haider","year":"2024","journal-title":"Biophys. J."},{"key":"ref_311","doi-asserted-by":"crossref","unstructured":"Li, H.-Y., Yeh, P.-A., Chiu, H.-C., Tang, C.-Y., and Tu, B.P. (2011). Hyperphosphorylation as a Defense Mechanism to Reduce TDP-43 Aggregation. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023075"},{"key":"ref_312","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1111\/j.1471-4159.2010.07098.x","article-title":"Regulation of TDP-43 Aggregation by Phosphorylation Andp62\/SQSTM1","volume":"116","author":"Brady","year":"2011","journal-title":"J. Neurochem."},{"key":"ref_313","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1021\/acs.chemrev.7b00305","article-title":"Electrostatic Interactions in Protein Structure, Folding, Binding, and Condensation","volume":"118","author":"Zhou","year":"2018","journal-title":"Chem. Rev."},{"key":"ref_314","doi-asserted-by":"crossref","first-page":"19164","DOI":"10.1074\/jbc.M114.561704","article-title":"UBE2E Ubiquitin-Conjugating Enzymes and Ubiquitin Isopeptidase Y Regulate TDP-43 Protein Ubiquitination","volume":"289","author":"Hans","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_315","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/S0021-9258(17)49926-1","article-title":"Multiple Distinct Pathways Lead to Hyperubiquitylated Insoluble TDP-43 Protein Independent of Its Translocation into Stress Granules","volume":"295","author":"Hans","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_316","doi-asserted-by":"crossref","first-page":"4103","DOI":"10.1074\/jbc.M112.419945","article-title":"Parkin Ubiquitinates Tar-DNA Binding Protein-43 (TDP-43) and Promotes Its Cytosolic Accumulation via Interaction with Histone Deacetylase 6 (HDAC6)","volume":"288","author":"Hebron","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_317","doi-asserted-by":"crossref","first-page":"16083","DOI":"10.1074\/jbc.RA118.003440","article-title":"Identification and Characterization of Ubiquitinylation Sites in TAR DNA-Binding Protein of 43 KDa (TDP-43)","volume":"293","author":"Hans","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_318","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1074\/mcp.M800390-MCP200","article-title":"Multiplex SILAC Analysis of a Cellular TDP-43 Proteinopathy Model Reveals Protein Inclusions Associated with SUMOylation and Diverse Polyubiquitin Chains","volume":"9","author":"Seyfried","year":"2010","journal-title":"Mol. Cell. Proteom."},{"key":"ref_319","doi-asserted-by":"crossref","first-page":"3483","DOI":"10.1093\/bioinformatics\/btv403","article-title":"JASSA: A Comprehensive Tool for Prediction of SUMOylation Sites and SIMs","volume":"31","author":"Beauclair","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_320","doi-asserted-by":"crossref","first-page":"3409","DOI":"10.1002\/pmic.200800646","article-title":"Systematic Study of Protein Sumoylation: Development of a Site-specific Predictor of SUMOsp 2.0","volume":"9","author":"Ren","year":"2009","journal-title":"Proteomics"},{"key":"ref_321","doi-asserted-by":"crossref","first-page":"W254","DOI":"10.1093\/nar\/gkl207","article-title":"SUMOsp: A Web Server for Sumoylation Site Prediction","volume":"34","author":"Xue","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_322","doi-asserted-by":"crossref","first-page":"W325","DOI":"10.1093\/nar\/gku383","article-title":"GPS-SUMO: A Tool for the Prediction of Sumoylation Sites and SUMO-Interaction Motifs","volume":"42","author":"Zhao","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_323","doi-asserted-by":"crossref","first-page":"14109","DOI":"10.1038\/ncomms14109","article-title":"Uncovering the SUMOylation and Ubiquitylation Crosstalk in Human Cells Using Sequential Peptide Immunopurification","volume":"8","author":"Lamoliatte","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_324","doi-asserted-by":"crossref","first-page":"rs2","DOI":"10.1126\/scisignal.2005146","article-title":"Proteome-Wide Identification of SUMO2 Modification Sites","volume":"7","author":"Tammsalu","year":"2014","journal-title":"Sci. Signal."},{"key":"ref_325","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.molcel.2012.02.017","article-title":"The RanBP2\/RanGAP1\u2217SUMO1\/Ubc9 Complex Is a Multisubunit SUMO E3 Ligase","volume":"46","author":"Werner","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_326","doi-asserted-by":"crossref","first-page":"6498","DOI":"10.1128\/MCB.22.18.6498-6508.2002","article-title":"Enzymes of the SUMO Modification Pathway Localize to Filaments of the Nuclear Pore Complex","volume":"22","author":"Zhang","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"ref_327","first-page":"1","article-title":"PML, SUMO, and RNF4: Guardians of Nuclear Protein Quality","volume":"55","author":"Muller","year":"2014","journal-title":"Mol. Cell"},{"key":"ref_328","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.ceb.2018.03.011","article-title":"PML Nuclear Bodies: From Architecture to Function","volume":"52","year":"2018","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_329","doi-asserted-by":"crossref","first-page":"6252","DOI":"10.1074\/jbc.275.9.6252","article-title":"Functional Heterogeneity of Small Ubiquitin-Related Protein Modifiers SUMO-1 versus SUMO-2\/3","volume":"275","author":"Saitoh","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_330","doi-asserted-by":"crossref","first-page":"35368","DOI":"10.1074\/jbc.M104214200","article-title":"Polymeric Chains of SUMO-2 and SUMO-3 Are Conjugated to Protein Substrates by SAE1\/SAE2 and Ubc9","volume":"276","author":"Tatham","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_331","doi-asserted-by":"crossref","unstructured":"Wang, W., and Matunis, M.J. (2023). Paralogue-Specific Roles of SUMO1 and SUMO2\/3 in Protein Quality Control and Associated Diseases. Cells, 13.","DOI":"10.3390\/cells13010008"},{"key":"ref_332","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.celrep.2018.12.027","article-title":"SUMOylation and the HSF1-Regulated Chaperone Network Converge to Promote Proteostasis in Response to Heat Shock","volume":"26","author":"Liebelt","year":"2019","journal-title":"Cell Rep."},{"key":"ref_333","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13024-025-00826-z","article-title":"A Stress-Dependent TDP-43 SUMOylation Program Preserves Neuronal Function 2024","volume":"20","author":"Suk","year":"2024","journal-title":"Mol. Neurodegener."},{"key":"ref_334","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1126\/science.aar7366","article-title":"RNA Buffers the Phase Separation Behavior of Prion-like RNA Binding Proteins","volume":"360","author":"Maharana","year":"2018","journal-title":"Science"},{"key":"ref_335","doi-asserted-by":"crossref","first-page":"e67605","DOI":"10.7554\/eLife.67605","article-title":"The Cooperative Binding of TDP-43 to GU-Rich RNA Repeats Antagonizes TDP-43 Aggregation","volume":"10","author":"Steiner","year":"2021","journal-title":"eLife"},{"key":"ref_336","doi-asserted-by":"crossref","first-page":"168751","DOI":"10.1016\/j.jmb.2024.168751","article-title":"Single Acetylation-Mimetic Mutation in TDP-43 Nuclear Localization Signal Disrupts Importin A1\/\u03b2 Signaling","volume":"436","author":"Ko","year":"2024","journal-title":"J. Mol. Biol."},{"key":"ref_337","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1038\/s41467-022-28822-7","article-title":"Sirtuin-1 Sensitive Lysine-136 Acetylation Drives Phase Separation and Pathological Aggregation of TDP-43","volume":"13","author":"Hans","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_338","doi-asserted-by":"crossref","first-page":"5845","DOI":"10.1038\/ncomms6845","article-title":"An Acetylation Switch Controls TDP-43 Function and Aggregation Propensity","volume":"6","author":"Cohen","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_339","doi-asserted-by":"crossref","first-page":"eabb4309","DOI":"10.1126\/science.abb4309","article-title":"HSP70 Chaperones RNA-Free TDP-43 into Anisotropic Intranuclear Liquid Spherical Shells","volume":"371","author":"Yu","year":"2021","journal-title":"Science"},{"key":"ref_340","doi-asserted-by":"crossref","unstructured":"Farina, S., Esposito, F., Battistoni, M., Biamonti, G., and Francia, S. (2021). Post-Translational Modifications Modulate Proteinopathies of TDP-43, FUS and HnRNP-A\/B in Amyotrophic Lateral Sclerosis. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.693325"},{"key":"ref_341","doi-asserted-by":"crossref","first-page":"eaaf7329","DOI":"10.1126\/scisignal.aaf7329","article-title":"Proteome-Wide Analysis of Arginine Monomethylation Reveals Widespread Occurrence in Human Cells","volume":"9","author":"Larsen","year":"2016","journal-title":"Sci. Signal."},{"key":"ref_342","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1074\/mcp.M115.053280","article-title":"Quantitative Profiling of the Activity of Protein Lysine Methyltransferase SMYD2 Using SILAC-Based Proteomics","volume":"15","author":"Olsen","year":"2016","journal-title":"Mol. Cell. Proteom."},{"key":"ref_343","doi-asserted-by":"crossref","first-page":"3532","DOI":"10.1074\/mcp.M113.031310","article-title":"Proteolytic Post-Translational Modification of Proteins: Proteomic Tools and Methodology","volume":"12","author":"Rogers","year":"2013","journal-title":"Mol. Cell. Proteom."},{"key":"ref_344","doi-asserted-by":"crossref","first-page":"6183","DOI":"10.1038\/ncomms7183","article-title":"The Cleavage Pattern of TDP-43 Determines Its Rate of Clearance and Cytotoxicity","volume":"6","author":"Li","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_345","doi-asserted-by":"crossref","first-page":"12390","DOI":"10.1038\/s41598-018-29658-2","article-title":"Tdp-25 Routing to Autophagy and Proteasome Ameliorates Its Aggregation in Amyotrophic Lateral Sclerosis Target Cells","volume":"8","author":"Cicardi","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_346","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.amjmed.2014.12.010","article-title":"Colchicine: Old and New","volume":"128","author":"Slobodnick","year":"2015","journal-title":"Am. J. Med."},{"key":"ref_347","doi-asserted-by":"crossref","first-page":"22827","DOI":"10.1038\/srep22827","article-title":"Transcriptional Induction of the Heat Shock Protein B8 Mediates the Clearance of Misfolded Proteins Responsible for Motor Neuron Diseases","volume":"6","author":"Crippa","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_348","doi-asserted-by":"crossref","first-page":"fcae304","DOI":"10.1093\/braincomms\/fcae304","article-title":"Colchicine Treatment in Amyotrophic Lateral Sclerosis: Safety, Biological and Clinical Effects in a Randomized Clinical Trial","volume":"6","author":"Gianferrari","year":"2024","journal-title":"Brain Commun."},{"key":"ref_349","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1007\/s13311-022-01247-2","article-title":"Antisense Oligonucleotides for the Study and Treatment of ALS","volume":"19","author":"Boros","year":"2022","journal-title":"Neurotherapeutics"},{"key":"ref_350","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1056\/NEJMoa2204705","article-title":"Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS","volume":"387","author":"Miller","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_351","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/s41593-017-0022-z","article-title":"Reducing the RNA Binding Protein TIA1 Protects against Tau-Mediated Neurodegeneration in Vivo","volume":"21","author":"Apicco","year":"2018","journal-title":"Nat. Neurosci."},{"key":"ref_352","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/nature22038","article-title":"Therapeutic Reduction of Ataxin-2 Extends Lifespan and Reduces Pathology in TDP-43 Mice","volume":"544","author":"Becker","year":"2017","journal-title":"Nature"},{"key":"ref_353","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.neuron.2016.04.006","article-title":"Gain of Toxicity from ALS\/FTD-Linked Repeat Expansions in C9ORF72 Is Alleviated by Antisense Oligonucleotides Targeting GGGGCC-Containing RNAs","volume":"90","author":"Jiang","year":"2016","journal-title":"Neuron"},{"key":"ref_354","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/s41591-021-01615-z","article-title":"Antisense Oligonucleotide Silencing of FUS Expression as a Therapeutic Approach in Amyotrophic Lateral Sclerosis","volume":"28","author":"Korobeynikov","year":"2022","journal-title":"Nat. Med."},{"key":"ref_355","doi-asserted-by":"crossref","unstructured":"Hwang, J.-T., Lee, A., and Kho, C. (2022). Ubiquitin and Ubiquitin-like Proteins in Cancer, Neurodegenerative Disorders, and Heart Diseases. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23095053"},{"key":"ref_356","doi-asserted-by":"crossref","first-page":"2951","DOI":"10.15252\/embj.201696394","article-title":"Phosphorylation of the FUS Low-complexity Domain Disrupts Phase Separation, Aggregation, and Toxicity","volume":"36","author":"Monahan","year":"2017","journal-title":"EMBO J."},{"key":"ref_357","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/jnc.13643","article-title":"Global SUMO Ylation Facilitates the Multimodal Neuroprotection Afforded by Quercetin against the Deleterious Effects of Oxygen\/Glucose Deprivation and the Restoration of Oxygen\/Glucose","volume":"138","author":"Lee","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_358","doi-asserted-by":"crossref","first-page":"415","DOI":"10.4103\/1673-5374.228718","article-title":"Drugging SUMOylation for Neuroprotection and Oncotherapy","volume":"13","author":"Bernstock","year":"2018","journal-title":"Neural Regen. Res."},{"key":"ref_359","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.bmcl.2017.12.028","article-title":"Small Molecule SUMOylation Activators Are Novel Neuroprotective Agents","volume":"28","author":"Krajnak","year":"2018","journal-title":"Bioorg. Med. Chem. Lett."}],"updated-by":[{"DOI":"10.3390\/cells15121053","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000}}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/10\/680\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T17:20:51Z","timestamp":1781198451000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/10\/680"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,8]]},"references-count":359,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["cells14100680"],"URL":"https:\/\/doi.org\/10.3390\/cells14100680","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,8]]}}}