{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T05:13:09Z","timestamp":1773637989818,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,1]],"date-time":"2024-09-01T00:00:00Z","timestamp":1725148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ARSLA foundation (France)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Abnormal cytoplasmic aggregates containing the TDP-43 protein and its fragments are present in the central nervous system of the majority of patients with amyotrophic lateral sclerosis (ALS) and in patients with frontotemporal lobar degeneration (FTLD). Many studies have focused on the C-terminal cleavage products of TDP-43 (CTFs), but few have focused on the N-terminal products (NTFs), yet several works and their protein domain composition support the involvement of NTFs in pathophysiology. In the present study, we expressed six NTFs of TDP-43, normally generated in vivo by proteases or following the presence of pathogenic genetic truncating variants, in HEK-293T cells. The N-terminal domain (NTD) alone was not sufficient to produce aggregates. Fragments containing the NTD and all or part of the RRM1 domain produced nuclear aggregates without affecting cell viability. Only large fragments also containing the RRM2 domain, with or without the glycine-rich domain, produced cytoplasmic aggregates. Of these, only NTFs containing even a very short portion of the glycine-rich domain caused a reduction in cell viability. Our results provide insights into the involvement of different TDP-43 domains in the formation of nuclear or cytoplasmic aggregates and support the idea that work on the development of therapeutic molecules targeting TDP-43 must also take into account NTFs and, in particular, those containing even a small part of the glycine-rich domain.<\/jats:p>","DOI":"10.3390\/genes15091157","type":"journal-article","created":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T03:45:21Z","timestamp":1725248721000},"page":"1157","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["N-Terminal Fragments of TDP-43\u2014In Vitro Analysis and Implication in the Pathophysiology of Amyotrophic Lateral Sclerosis and Frontotemporal Lobar Degeneration"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5610-4947","authenticated-orcid":false,"given":"Anna","family":"Chami","sequence":"first","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Imaging Brain & Neuropsychiatry iBraiN U1253, Universit\u00e9 de Tours, 37032 Tours, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L\u00e9a","family":"Bedja-Iacona","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Imaging Brain & Neuropsychiatry iBraiN U1253, Universit\u00e9 de Tours, 37032 Tours, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elodie","family":"Richard","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Imaging Brain & Neuropsychiatry iBraiN U1253, Universit\u00e9 de Tours, 37032 Tours, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debora","family":"Lanznaster","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Imaging Brain & Neuropsychiatry iBraiN U1253, Universit\u00e9 de Tours, 37032 Tours, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7918-9755","authenticated-orcid":false,"given":"Sylviane","family":"Marouillat","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Imaging Brain & Neuropsychiatry iBraiN U1253, Universit\u00e9 de Tours, 37032 Tours, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4512-2303","authenticated-orcid":false,"given":"Charlotte","family":"Veyrat-Durebex","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Imaging Brain & Neuropsychiatry iBraiN U1253, Universit\u00e9 de Tours, 37032 Tours, France"},{"name":"CHU de Tours, Service de Biochimie et Biologie Mol\u00e9culaire, 37044 Tours, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Andres","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Imaging Brain & Neuropsychiatry iBraiN U1253, Universit\u00e9 de Tours, 37032 Tours, France"},{"name":"CHU de Tours, Service de Biochimie et Biologie Mol\u00e9culaire, 37044 Tours, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1625-8845","authenticated-orcid":false,"given":"Philippe","family":"Corcia","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Imaging Brain & Neuropsychiatry iBraiN U1253, Universit\u00e9 de Tours, 37032 Tours, France"},{"name":"CHU de Tours, Service de Neurologie, 37044 Tours, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e9l\u00e8ne","family":"Blasco","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Imaging Brain & Neuropsychiatry iBraiN U1253, Universit\u00e9 de Tours, 37032 Tours, France"},{"name":"CHU de Tours, Service de Biochimie et Biologie Mol\u00e9culaire, 37044 Tours, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Vourc\u2019h","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Imaging Brain & Neuropsychiatry iBraiN U1253, Universit\u00e9 de Tours, 37032 Tours, France"},{"name":"CHU de Tours, Service de Biochimie et Biologie Mol\u00e9culaire, 37044 Tours, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,1]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"102441","DOI":"10.1016\/j.arr.2024.102441","article-title":"TDP-43 Proteinopathy in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis: From Pathomechanisms to Therapeutic Strategies","volume":"100","author":"Ho","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1136\/jnnp-2020-325064","article-title":"Effect of Familial Clustering in the Genetic Screening of 235 French ALS Families","volume":"92","author":"Corcia","year":"2021","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Nijs, M., and Van Damme, P. (2024). The Genetics of Amyotrophic Lateral Sclerosis. Curr. Opin. Neurol.","DOI":"10.1097\/WCO.0000000000001294"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"148.e9","DOI":"10.1016\/j.neurobiolaging.2020.07.014","article-title":"Underlying Genetic Variation in Familial Frontotemporal Dementia: Sequencing of 198 Patients","volume":"97","author":"Mol","year":"2021","journal-title":"Neurobiol. Aging"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/ng.132","article-title":"TARDBP Mutations in Individuals with Sporadic and Familial Amyotrophic Lateral Sclerosis","volume":"40","author":"Kabashi","year":"2008","journal-title":"Nat. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1126\/science.1154584","article-title":"TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis","volume":"319","author":"Sreedharan","year":"2008","journal-title":"Science"},{"key":"ref_8","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_9","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_10","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_11","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_12","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1080\/21678421.2017.1349152","article-title":"Mutation in the RRM2 Domain of TDP-43 in Amyotrophic Lateral Sclerosis with Rapid Progression Associated with Ubiquitin Positive Aggregates in Cultured Motor Neurons","volume":"19","author":"Maurel","year":"2018","journal-title":"Amyotroph. Lateral Scler. Frontotemporal Degener."},{"key":"ref_13","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_14","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1002\/ana.21147","article-title":"Pathological TDP-43 Distinguishes Sporadic Amyotrophic Lateral Sclerosis from Amyotrophic Lateral Sclerosis with SOD1 Mutations","volume":"61","author":"Mackenzie","year":"2007","journal-title":"Ann. Neurol."},{"key":"ref_15","first-page":"86","article-title":"TDP-43 Proteinopathies: A New Wave of Neurodegenerative Diseases","volume":"92","author":"Orie","year":"2020","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_16","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_17","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/s41583-021-00477-1","article-title":"TDP43 Aggregates: The \u201cSchr\u00f6dinger\u2019s Cat\u201d in Amyotrophic Lateral Sclerosis","volume":"22","author":"Lanznaster","year":"2021","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1093\/brain\/awz078","article-title":"The Debated Toxic Role of Aggregated TDP-43 in Amyotrophic Lateral Sclerosis: A Resolution in Sight?","volume":"142","author":"Hergesheimer","year":"2019","journal-title":"Brain"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"19437","DOI":"10.1074\/jbc.M116.737726","article-title":"Quantification of the Relative Contributions of Loss-of-Function and Gain-of-Function Mechanisms in TAR DNA-Binding Protein 43 (TDP-43) Proteinopathies","volume":"291","author":"Cascella","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kitamura, A., Nakayama, Y., Shibasaki, A., Taki, A., Yuno, S., Takeda, K., Yahara, M., Tanabe, N., and Kinjo, M. (2016). Interaction of RNA with a C-Terminal Fragment of the Amyotrophic Lateral Sclerosis-Associated TDP43 Reduces Cytotoxicity. Sci. Rep., 6.","DOI":"10.1038\/srep19230"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Cicardi, M.E., Cristofani, R., Rusmini, P., Meroni, M., Ferrari, V., Vezzoli, G., Tedesco, B., Piccolella, M., Messi, E., and Galbiati, M. (2018). Tdp-25 Routing to Autophagy and Proteasome Ameliorates Its Aggregation in Amyotrophic Lateral Sclerosis Target Cells. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-29658-2"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Berning, B.A., and Walker, A.K. (2019). The Pathobiology of TDP-43 C-Terminal Fragments in ALS and FTLD. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.00335"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1096\/fj.01-0995fje","article-title":"Preferential Transformation of Human Neuronal Cells by Human Adenoviruses and the Origin of HEK 293 Cells","volume":"16","author":"Shaw","year":"2002","journal-title":"FASEB J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1080\/21678421.2020.1752243","article-title":"A Novel Mutation in the Cleavage Site N291 of TDP-43 Protein in a Familial Case of Amyotrophic Lateral Sclerosis","volume":"21","author":"Chami","year":"2020","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"10530","DOI":"10.1523\/JNEUROSCI.3421-07.2007","article-title":"Progranulin Mediates Caspase-Dependent Cleavage of TAR DNA Binding Protein-43","volume":"27","author":"Zhang","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kametani, F., Obi, T., Shishido, T., Akatsu, H., Murayama, S., Saito, Y., Yoshida, M., and Hasegawa, M. (2016). Mass Spectrometric Analysis of Accumulated TDP-43 in Amyotrophic Lateral Sclerosis Brains. Sci. Rep., 6.","DOI":"10.1038\/srep23281"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"13171","DOI":"10.1074\/jbc.M110.197483","article-title":"TDP-43-Induced Death Is Associated with Altered Regulation of BIM and Bcl-xL and Attenuated by Caspase-Mediated TDP-43 Cleavage","volume":"286","author":"Suzuki","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_28","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_29","doi-asserted-by":"crossref","first-page":"182","DOI":"10.2353\/ajpath.2008.080003","article-title":"Enrichment of C-Terminal Fragments in TAR DNA-Binding Protein-43 Cytoplasmic Inclusions in Brain but Not in Spinal Cord of Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis","volume":"173","author":"Igaz","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_30","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":"Human. Molecular Genetics"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1038\/jcbfm.2014.105","article-title":"Dual Vulnerability of TDP-43 to Calpain and Caspase-3 Proteolysis after Neurotoxic Conditions and Traumatic Brain Injury","volume":"34","author":"Yang","year":"2014","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"8516","DOI":"10.1074\/jbc.M809462200","article-title":"Expression of TDP-43 C-Terminal Fragments in Vitro Recapitulates Pathological Features of TDP-43 Proteinopathies","volume":"284","author":"Igaz","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"121","DOI":"10.15252\/embj.201591998","article-title":"TDP-43 Loss of Function Increases TFEB Activity and Blocks Autophagosome-Lysosome Fusion","volume":"35","author":"Xia","year":"2015","journal-title":"EMBO J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1038\/ncomms2303","article-title":"A Role for Calpain-Dependent Cleavage of TDP-43 in Amyotrophic Lateral Sclerosis Pathology","volume":"3","author":"Yamashita","year":"2012","journal-title":"Nat. Commun."},{"key":"ref_35","first-page":"E1121","article-title":"Partial Loss of TDP-43 Function Causes Phenotypes of Amyotrophic Lateral Sclerosis","volume":"111","author":"Yang","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1002\/pmic.201200006","article-title":"Asparaginyl Endopeptidase Cleaves TDP-43 in Brain","volume":"12","author":"Herskowitz","year":"2012","journal-title":"Proteomics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1093\/molbev\/msp259","article-title":"SeaView Version 4: A Multiplatform Graphical User Interface for Sequence Alignment and Phylogenetic Tree Building","volume":"27","author":"Gouy","year":"2010","journal-title":"Mol. Biol. Evol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"D439","DOI":"10.1093\/nar\/gkab1061","article-title":"AlphaFold Protein Structure Database: Massively Expanding the Structural Coverage of Protein-Sequence Space with High-Accuracy Models","volume":"50","author":"Varadi","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly Accurate Protein Structure Prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Furukawa, Y., Suzuki, Y., Fukuoka, M., Nagasawa, K., Nakagome, K., Shimizu, H., Mukaiyama, A., and Akiyama, S. (2016). A Molecular Mechanism Realizing Sequence-Specific Recognition of Nucleic Acids by TDP-43. Sci. Rep., 6.","DOI":"10.1038\/srep20576"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1136\/jmg.2008.062463","article-title":"Contribution of TARDBP Mutations to Sporadic Amyotrophic Lateral Sclerosis","volume":"46","author":"Daoud","year":"2009","journal-title":"J. Med. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1093\/brain\/awx082","article-title":"A Comprehensive Analysis of Rare Genetic Variation in Amyotrophic Lateral Sclerosis in the UK","volume":"140","author":"Morgan","year":"2017","journal-title":"Brain"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e13104","DOI":"10.1111\/bpa.13104","article-title":"Atypical TDP-43 Protein Expression in an ALS Pedigree Carrying a p.Y374X Truncation Mutation in TARDBP","volume":"33","author":"Julian","year":"2023","journal-title":"Brain Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41467-017-00062-0","article-title":"Functional and Dynamic Polymerization of the ALS-Linked Protein TDP-43 Antagonizes Its Pathologic Aggregation","volume":"8","author":"Afroz","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Jiang, L.-L., Xue, W., Hong, J.-Y., Zhang, J.-T., Li, M.-J., Yu, S.-N., He, J.-H., and Hu, H.-Y. (2017). The N-Terminal Dimerization Is Required for TDP-43 Splicing Activity. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-06263-3"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"102459","DOI":"10.1016\/j.isci.2021.102459","article-title":"Molecular, Functional, and Pathological Aspects of TDP-43 Fragmentation","volume":"24","author":"Chhangani","year":"2021","journal-title":"iScience"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.brainres.2016.04.069","article-title":"The Extreme N-Terminus of TDP-43 Mediates the Cytoplasmic Aggregation of TDP-43 and Associated Toxicity in Vivo","volume":"1647","author":"Sasaguri","year":"2016","journal-title":"Brain Res."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Pinarbasi, E.S., Ca\u011fatay, T., Fung, H.Y.J., Li, Y.C., Chook, Y.M., and Thomas, P.J. (2018). Active Nuclear Import and Passive Nuclear Export Are the Primary Determinants of TDP-43 Localization. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-25008-4"},{"key":"ref_49","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."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/9\/1157\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:46:41Z","timestamp":1760111201000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/9\/1157"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,1]]},"references-count":49,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["genes15091157"],"URL":"https:\/\/doi.org\/10.3390\/genes15091157","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,1]]}}}