{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:29:22Z","timestamp":1790393362230,"version":"4.1.0"},"reference-count":224,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,13]],"date-time":"2021-03-13T00:00:00Z","timestamp":1615593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Amyotrophic lateral sclerosis (ALS) is a devastating, uniformly lethal progressive degenerative disorder of motor neurons that overlaps with frontotemporal lobar degeneration (FTLD) clinically, morphologically, and genetically. Although many distinct mutations in various genes are known to cause amyotrophic lateral sclerosis, it remains poorly understood how they selectively impact motor neuron biology and whether they converge on common pathways to cause neuronal degeneration. Many of the gene mutations are in proteins that share similar functions. They can be grouped into those associated with cell axon dynamics and those associated with cellular phagocytic machinery, namely protein aggregation and metabolism, apoptosis, and intracellular nucleic acid transport. Analysis of pathways implicated by mutant ALS genes has provided new insights into the pathogenesis of both familial forms of ALS (fALS) and sporadic forms (sALS), although, regrettably, this has not yet yielded definitive treatments. Many genes play an important role, with TARDBP, SQSTM1, VCP, FUS, TBK1, CHCHD10, and most importantly, C9orf72 being critical genetic players in these neurological disorders. In this mini-review, we will focus on the molecular mechanisms of these two diseases.<\/jats:p>","DOI":"10.3390\/diagnostics11030509","type":"journal-article","created":{"date-parts":[[2021,3,14]],"date-time":"2021-03-14T22:13:10Z","timestamp":1615759990000},"page":"509","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Amyotrophic Lateral Sclerosis and Frontotemporal Lobar Degenerations: Similarities in Genetic Background"],"prefix":"10.3390","volume":"11","author":[{"given":"Eva","family":"Parobkova","sequence":"first","affiliation":[{"name":"Department of Pathology and Molecular Medicine, Third Faculty of Medicine, Charles University and Thomayer University Hospital, 14059 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6152-6343","authenticated-orcid":false,"given":"Radoslav","family":"Matej","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, Third Faculty of Medicine, Charles University and Thomayer University Hospital, 14059 Prague, Czech Republic"},{"name":"Department of Pathology, First Faculty of Medicine, Charles University, and General University Hospital, 14059 Prague, Czech Republic"},{"name":"Department of Pathology, Third Faculty of Medicine, Charles University, and University Hospital Kralovske Vinohrady, 14059 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1038\/nn.3357","article-title":"Degeneration and impaired regeneration of gray matter oligodendrocytes in amyotrophic lateral sclerosis","volume":"5","author":"Kang","year":"2013","journal-title":"Nat. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1080\/21678421.2017.1369125","article-title":"July 2017 ENCALS statement on edaravone","volume":"18","author":"Andersen","year":"2017","journal-title":"Amyotroph Lateral Scler Front. Degener."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1056\/NEJM200105313442207","article-title":"Amyotrophic lateral sclerosis","volume":"22","author":"Rowland","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_4","first-page":"e802","article-title":"ALS phenotype is influenced by age, sex, and genetics: A population-based study","volume":"8","author":"Moglia","year":"2020","journal-title":"Neurology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/nrneurol.2011.150","article-title":"Clinical genetics of amyotrophic lateral sclerosis: What do we really know?","volume":"11","author":"Andersen","year":"2011","journal-title":"Nat. Rev. Neurol."},{"key":"ref_6","first-page":"623","article-title":"Rate of familial amyotrophic lateral sclerosis: A systematic review and meta-analysis","volume":"6","author":"Yrne","year":"2011","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1242\/bio.201410066","article-title":"A genetic screen identifies Tor as an interactor of VAPB in a Drosophila model of amyotrophic lateral sclerosis","volume":"11","author":"Deivasigamani","year":"2014","journal-title":"Biol. Open"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/nrneurol.2011.153","article-title":"Clinical diagnosis and management of amyotrophic lateral sclerosis","volume":"11","author":"Hardiman","year":"2011","journal-title":"Nat. Rev. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/S0140-6736(10)61156-7","article-title":"Amyotrophic lateral sclerosis","volume":"377","author":"Kiernan","year":"2011","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.tig.2018.03.001","article-title":"ALS Genes in the Genomic Era and their Implications for FTD","volume":"34","author":"Nguyen","year":"2018","journal-title":"Trends Genet."},{"key":"ref_11","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_12","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1212\/01.WNL.0000078928.20107.52","article-title":"Survival in frontotemporal dementia","volume":"61","author":"Hodges","year":"2003","journal-title":"Neurology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s00401-011-0839-6","article-title":"Neuropathological background of phenotypical variability in frontotemporal dementia","volume":"122","author":"Josephs","year":"2011","journal-title":"Acta Neuropathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/j.1468-1331.2009.02717.x","article-title":"Relationship between ALS and the degree of cognitive impairment, markers of neurodegeneration and predictors for poor outcome. A prospective study","volume":"17","author":"Rusina","year":"2010","journal-title":"Eur. J. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1212\/WNL.0b013e3181bf997a","article-title":"The heritability and genetics of frontotemporal lobar degeneration","volume":"73","author":"Rohrer","year":"2009","journal-title":"Neurology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1093\/brain\/awm024","article-title":"TDP-43 pathology in familial frontotemporal dementia and motor neuron disease without Progranulin mutations","volume":"130","author":"Seelaar","year":"2007","journal-title":"Brain"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"817","DOI":"10.3109\/07853890.2012.665471","article-title":"The molecular basis of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum","volume":"44","year":"2012","journal-title":"Ann. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.tins.2013.04.010","article-title":"Current insights into the C9 or f72 repeat expansion diseases of the FTLD\/ALS spectrum","volume":"36","author":"Cruts","year":"2013","journal-title":"Trends Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e9","DOI":"10.1016\/j.neurobiolaging.2016.12.008","article-title":"Investigating the role of ALS genes CHCHD10 and TUBA4A in Belgian FTD-ALS spectrum patients","volume":"51","author":"Perrone","year":"2017","journal-title":"Neurobiol. Aging"},{"key":"ref_20","first-page":"1094","article-title":"Are amyotrophic lateral sclerosis patients cognitively normal?","volume":"8","author":"Murphy","year":"2003","journal-title":"Neurology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1212\/01.wnl.0000172911.39167.b6","article-title":"Prevalence and patterns of cognitive impairment in sporadic ALS","volume":"65","author":"Ringholz","year":"2005","journal-title":"Neurology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1016\/j.jocn.2009.03.005","article-title":"Frontotemporal dementia and motor neurone disease: Overlapping clinic-pathological disorders","volume":"9","author":"Lillo","year":"2009","journal-title":"J. Clin. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1212\/WNL.51.6.1546","article-title":"Frontotemporal lobar degeneration: A consensus on clinical diagnostic criteria","volume":"51","author":"Neary","year":"1998","journal-title":"Neurology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000112894","article-title":"Frontotemporal dementia: Its rediscovery","volume":"8","author":"Pasquier","year":"1997","journal-title":"Eur. Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"171","DOI":"10.4103\/2152-7806.169561","article-title":"A comprehensive review of amyotrophic lateral sclerosis","volume":"6","author":"Zarei","year":"2015","journal-title":"Surg. Neurol. Int."},{"key":"ref_26","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_27","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.3389\/fnins.2019.01310","article-title":"ALS Genetics, Mechanisms, and Therapeutics: Where Are We Now?","volume":"13","author":"Mejzini","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s40478-017-0480-2","article-title":"Distinct TDP-43 inclusion morphologies in frontotemporal lobar degeneration with and without amyotrophic lateral sclerosis","volume":"5","author":"Tan","year":"2017","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s00401-011-0845-8","article-title":"A harmonized classification system for FTLD-TDP pathology","volume":"122","author":"Mackenzie","year":"2011","journal-title":"Acta Neuropathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1093\/brain\/aws004","article-title":"Characterization of frontotemporal dementia and\/or amyotrophic lateral sclerosis associated with the GGGGCC repeat expansion in C9ORF72","volume":"3","author":"Boeve","year":"2012","journal-title":"Brain"},{"key":"ref_31","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_32","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13041-017-0287-x","article-title":"TBK1: A new player in ALS linking autophagy and neuroinflammation","volume":"10","author":"Oakes","year":"2017","journal-title":"Mol. Brain"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1001\/archneur.58.11.1803","article-title":"Clinical and pathological diagnosis of frontotemporal dementia: Report of the Work Group on Frontotemporal Dementia and Pick\u2019s Disease. Clinical and pathological diagnosis of frontotemporal dementia: Report of the Work Group on Frontotemporal Dementia and Pick\u2018s Disease","volume":"58","author":"McKhann","year":"2001","journal-title":"Arch. Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/0304-3940(88)90081-X","article-title":"Ubiquitin deposits in anterior horn cells in motor neurone disease","volume":"93","author":"Leigh","year":"1988","journal-title":"Neurosci. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1126\/science.1166066","article-title":"Mutations in the FUS\/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis","volume":"323","author":"Kwiatkowski","year":"2009","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1126\/science.1165942","article-title":"Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6","volume":"323","author":"Vance","year":"2009","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1002\/ana.21154","article-title":"TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer\u2018s disease","volume":"61","author":"Lin","year":"2007","journal-title":"Ann. Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1097\/NEN.0b013e31817713b5","article-title":"Concomitant TAR-DNA-binding protein 43 pathology is present in Alzheimer disease and corticobasal degeneration but not in other tauopathies","volume":"67","author":"Uryu","year":"2008","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.brainres.2007.09.048","article-title":"Concurrence of TDP-43, tau and alpha-synuclein pathology in brains of Alzheimer\u2018s disease and dementia with Lewy bodies","volume":"1184","author":"Higashi","year":"2007","journal-title":"Brain Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1007\/s00401-010-0731-9","article-title":"Effect of topographical distribution of \u03b1-synuclein pathology on TDP-43 accumulation in Lewy body disease","volume":"120","author":"Yokota","year":"2010","journal-title":"Acta Neuropathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1007\/s00415-009-5069-7","article-title":"Amyotrophic lateral sclerosis, frontotemporal dementia and beyond: The TDP-43 diseases","volume":"256","author":"Geser","year":"2009","journal-title":"J. Neurol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1850","DOI":"10.1212\/01.wnl.0000304041.09418.b1","article-title":"Abnormal TDP-43 immunoreactivity in AD modifies clinicopathologic and radiologic phenotype","volume":"70","author":"Josephs","year":"2008","journal-title":"Neurology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3062","DOI":"10.1007\/s12035-016-9850-1","article-title":"C9ORF72 Regulates Stress Granule Formation and Its Deficiency Impairs Stress Granule Assembly, Hypersensitizing Cells to Stress","volume":"54","author":"Maharjan","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_44","first-page":"324","article-title":"C9orf72 is required for proper macrophage and microglial function in mice","volume":"351","author":"Bogdanik","year":"2016","journal-title":"Science"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s40478-016-0324-5","article-title":"The ALS\/FTLD associated protein C9orf72 associates with SMCR8 and WDR41 to regulate the autophagy-lysosome pathway","volume":"4","author":"Sullivan","year":"2016","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1002\/stem.2388","article-title":"C9orf72 Hexanucleotide Expansions Are Associated with Altered Endoplasmic Reticulum Calcium Homeostasis and Stress Granule Formation in Induced Pluripotent Stem Cell-Derived Neurons from Patients with Amyotrophic Lateral Sclerosis and Frontotemporal Dementia","volume":"34","author":"Dafinca","year":"2016","journal-title":"Stem Cells"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"24131","DOI":"10.1074\/jbc.M702824200","article-title":"p62\/SQSTM1 binds directly to Atg8\/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy","volume":"282","author":"Pankiv","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2","DOI":"10.2174\/1567205012666141218123202","article-title":"The contribution of proteinase-activated receptors to intracellular signaling, transcellular transport and autophagy in Alzheimer\u2018s disease","volume":"12","author":"Rohan","year":"2015","journal-title":"Curr. Alzheimer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s11658-016-0031-z","article-title":"p62 links the autophagy pathway and the ubiqutin-proteasome system upon ubiquitinated protein degradation","volume":"21","author":"Liu","year":"2016","journal-title":"Cell Mol. Biol. Lett."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.bbamcr.2012.11.004","article-title":"A role for sequestosome 1\/p62 in mitochondrial dynamics, import and genome integrity","volume":"1833","author":"Seibenhener","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1212\/WNL.0b013e31826e25df","article-title":"SQSTM1 mutations in frontotemporal lobar degeneration and amyotrophic lateral sclerosis","volume":"79","author":"Rubino","year":"2012","journal-title":"Neurology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"9754","DOI":"10.1073\/pnas.0501957102","article-title":"Systematically perturbed folding patterns of amyotrophic lateral sclerosis (ALS)-associated SOD1 mutants","volume":"102","author":"Lindberg","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1172\/JCI71601","article-title":"Emerging mechanisms of molecular pathology in ALS","volume":"25","author":"Peters","year":"2015","journal-title":"J. Clin. Invest."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"26797","DOI":"10.3390\/ijms161125990","article-title":"The Function of Autophagy in Neurodegenerative Diseases","volume":"16","author":"Kiriyama","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1136\/jnnp-2018-319386","article-title":"Misfolded SOD1 inclusions in patients with mutations in C9orf72 and other ALS\/FTD-associated genes","volume":"90","author":"Forsberg","year":"2019","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.expneurol.2010.06.004","article-title":"Increased neuronal Rab5 immunoreactive endosomes do not colocalize with TDP-43 in motor neuron disease","volume":"225","author":"Matej","year":"2010","journal-title":"Exp. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/nrd3050","article-title":"Protein aggregation diseases: Pathogenicity and therapeutic perspectives","volume":"9","author":"Aguzzi","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/nature05292","article-title":"Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases","volume":"443","author":"Lin","year":"2006","journal-title":"Nature"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1007\/s00401-007-0299-1","article-title":"Mitochondrial alterations in dorsal root ganglion cells in sporadic amyotrophic lateral sclerosis","volume":"114","author":"Sasaki","year":"2007","journal-title":"Acta Neuropathol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1002\/ana.410420416","article-title":"Increased 3-nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis","volume":"42","author":"Beal","year":"1997","journal-title":"Ann. Neurol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"C641","DOI":"10.1152\/ajpcell.00222.2006","article-title":"Mitochondria and neuronal activity","volume":"292","author":"Kann","year":"2007","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1152\/physrev.2000.80.1.315","article-title":"Mitochondria and neuronal survival","volume":"80","author":"Nicholls","year":"2000","journal-title":"Physiol. Rev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3417","DOI":"10.1113\/jphysiol.2014.282517","article-title":"Non-signalling energy use in the brain","volume":"593","author":"Engl","year":"2015","journal-title":"J. Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/nrm3412","article-title":"Mitochondria as sensors and regulators of calcium signalling","volume":"13","author":"Rizzuto","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Deng, J., Yang, M., Chen, Y., Chen, X., Liu, J., Sun, S., Cheng, H., Li, Y., Bigio, E.H., and Mesulam, M. (2015). FUS Interacts with HSP60 to Promote Mitochondrial Damage. PLoS Genet., 11.","DOI":"10.1371\/journal.pgen.1005357"},{"key":"ref_66","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_67","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_68","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1093\/brain\/awu138","article-title":"A mitochondrial origin for frontotemporal dementia and amyotrophic lateral sclerosis through CHCHD10 involvement","volume":"137","author":"Bannwarth","year":"2014","journal-title":"Brain"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"58","DOI":"10.15252\/emmm.201505496","article-title":"CHCHD10 mutations promote loss of mitochondrial cristae junctions with impaired mitochondrial genome maintenance and inhibition of apoptosis","volume":"8","author":"Genin","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1016\/S0140-6736(11)61305-6","article-title":"Mitochondrial diseases","volume":"379","author":"Schapira","year":"2012","journal-title":"Lancet"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"E7701","DOI":"10.1073\/pnas.1611673113","article-title":"Two familial ALS proteins function in prevention\/repair of transcription-associated DNA damage","volume":"113","author":"Hill","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"24731","DOI":"10.1074\/jbc.M113.497974","article-title":"The RNA-binding protein fused in sarcoma (FUS) functions downstream of poly(ADP-ribose) polymerase (PARP) in response to DNA damage","volume":"288","author":"Mastrocola","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_73","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_74","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.molcel.2011.05.035","article-title":"The Ewing sarcoma protein regulates DNA damage-induced alternative splicing","volume":"43","author":"Paronetto","year":"2011","journal-title":"Mol. Cell"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.molcel.2011.04.026","article-title":"Human senataxin resolves RNA\/DNA hybrids formed at transcriptional pause sites to promote Xrn2-dependent termination","volume":"42","author":"Proudfoot","year":"2011","journal-title":"Mol. Cell"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1016\/j.celrep.2015.04.053","article-title":"A Systematic Analysis of Factors Localized to Damaged Chromatin Reveals PARP-Dependent Recruitment of Transcription Factors","volume":"11","author":"Izhar","year":"2011","journal-title":"Cell Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"355","DOI":"10.2478\/s13380-012-0044-7","article-title":"Pathologies of axonal transport in neurodegenerative diseases","volume":"3","author":"Liu","year":"2012","journal-title":"Transl. Neurosci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/nrn3380","article-title":"Axonal transport deficits and neurodegenerative diseases","volume":"14","author":"Millecamps","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.nbd.2017.02.004","article-title":"Neurobiology of axonal transport defects in motor neuron diseases: Opportunities for translational research?","volume":"105","author":"Hafezparast","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/s41582-019-0257-2","article-title":"Axonal transport and neurological disease","volume":"15","author":"Sleigh","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"ref_81","first-page":"29","article-title":"Axonal transport and neurodegenerative disease: Vesicle-motor complex formation and their regulation","volume":"4","author":"Anderson","year":"2014","journal-title":"Degener. Neurol. Neuromuscul. Dis."},{"key":"ref_82","first-page":"15","article-title":"Disruption of dynein\/dynactin inhibits axonal transport in motor neurons causing late-onset progressive degeneration","volume":"347","author":"Wallace","year":"2002","journal-title":"Neuron"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1002\/ana.20468","article-title":"Distal spinal and bulbar muscular atrophy caused by dynactin mutation","volume":"57","author":"Puls","year":"2005","journal-title":"Ann. Neurol."},{"key":"ref_84","first-page":"724","article-title":"Point mutations of the p150 subunit of dynactin (DCTN1) gene in ALS","volume":"637","author":"Sedlmeier","year":"2004","journal-title":"Neurology"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1083\/jcb.200408113","article-title":"A standardized kinesin nomenclature","volume":"167","author":"Lawrence","year":"2004","journal-title":"J. Cell Biol."},{"key":"ref_86","first-page":"204","article-title":"A Case for Microtubule Vulnerability in Amyotrophic Lateral Sclerosis: Altered Dynamics During Disease","volume":"13","author":"Clark","year":"2016","journal-title":"Front. Cell Neurosci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.neuron.2014.09.027","article-title":"Exome-wide rare variant analysis identifies TUBA4A mutations associated with familial ALS","volume":"84","author":"Smith","year":"2014","journal-title":"Neuron"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Cai, D., McEwen, D.P., Martens, J.R., Meyhofer, E., and Verhey, K.J. (2009). Single molecule imaging reveals differences in microtubule track selection between Kinesin motors. PLoS Biol., 7.","DOI":"10.1371\/journal.pbio.1000216"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.brainres.2018.02.018","article-title":"mRNP assembly, axonal transport, and local translation in neurodegenerative diseases","volume":"1693","author":"Khalil","year":"2018","journal-title":"Brain Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1042\/BCJ20160499","article-title":"RNA-binding proteins with prion-like domains in health and disease","volume":"474","author":"Harrison","year":"2017","journal-title":"Biochem. J."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nature20413","article-title":"Decoding ALS: From genes to mechanism","volume":"539","author":"Taylor","year":"2016","journal-title":"Nature"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"4334","DOI":"10.1073\/pnas.1017150108","article-title":"Active liquid-like behavior of nucleoli determines their size and shape in Xenopus laevis oocytes","volume":"108","author":"Brangwynne","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1073\/pnas.89.1.305","article-title":"U1 and U2 small nuclear RNAs are present in nuclear speckles","volume":"89","author":"Huang","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1126\/science.1082320","article-title":"Decapping and decay of messenger RNA occur in cytoplasmic processing bodies","volume":"300","author":"Sheth","year":"2003","journal-title":"Science"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3389\/fnmol.2020.00078","article-title":"Dysregulation of RNA-Binding Proteins in Amyotrophic Lateral Sclerosis","volume":"29","author":"Xue","year":"2020","journal-title":"Front. Mol. Neurosci."},{"key":"ref_96","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_97","doi-asserted-by":"crossref","unstructured":"Liu-Yesucevitz, L., Bilgutay, A., Zhang, Y.J., Vanderweyde, T., Citro, A., Mehta, T., Zaarur, N., McKee, A., Bowser, R., and Sherman, M. (2010). Tar DNA binding protein-43 (TDP-43) associates with stress granules: Analysis of cultured cells and pathological brain tissue. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013250"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.neuint.2012.01.019","article-title":"Endogenous TDP-43 localized to stress granules can subsequently form protein aggregates","volume":"60","author":"Parker","year":"2012","journal-title":"Neurochem. Int."},{"key":"ref_99","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_100","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_101","first-page":"46","article-title":"TDP-43 and FUS\/TLS: Emerging roles in RNA processing and neurodegeneration","volume":"5","author":"Polymenidou","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1016\/j.cell.2009.03.006","article-title":"Rethinking ALS: The FUS about TDP-43","volume":"136","author":"Cleveland","year":"2009","journal-title":"Cell"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.tins.2011.05.002","article-title":"TDP-43 and FUS: A nuclear affair","volume":"34","author":"Dormann","year":"2011","journal-title":"Trends Neurosci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"104639","DOI":"10.1016\/j.nbd.2019.104639","article-title":"Stress granule mediated protein aggregation and underlying gene defects in the FTD-ALS spectrum","volume":"134","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1007\/s00401-012-1045-x","article-title":"The RNA-binding motif 45 (RBM45) protein accumulates in inclusion bodies in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) patients","volume":"124","author":"Collins","year":"2012","journal-title":"Acta Neuropathol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1379\/1466-1268(2002)007<0213:VSTROE>2.0.CO;2","article-title":"Visibly stressed: The role of eIF2, TIA-1, and stress granules in protein translation","volume":"7","author":"Anderson","year":"2002","journal-title":"Cell Stress Chaperones"},{"key":"ref_107","first-page":"431","article-title":"RNA-binding proteins TIA-1 and TIAR link the phosphorylation of eIF-2 alpha to the assembly of mammalian stress granules","volume":"1471","author":"Kedersha","year":"1999","journal-title":"J. Cell Biol."},{"key":"ref_108","first-page":"537","article-title":"Neuroinflammation in motor neuron disease","volume":"77","author":"Komine","year":"2015","journal-title":"Nagoya J. Med. Sci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jns.2008.08.024","article-title":"Progranulin (PGRN) expression in ALS: An immunohistochemical study","volume":"276","author":"Irwin","year":"2009","journal-title":"J. Neurol. Sci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/nn.4000","article-title":"Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia","volume":"18","author":"Freischmidt","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"3250","DOI":"10.1172\/JCI90607","article-title":"Microglia and C9orf72 in neuroinflammation and ALS and frontotemporal dementia","volume":"127","author":"Lall","year":"2017","journal-title":"J. Clin. Invest."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1126\/science.1223813","article-title":"Host-gut microbiota metabolic interactions","volume":"336","author":"Nicholson","year":"2012","journal-title":"Science"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1038\/s41586-018-0119-x","article-title":"Microglial control of astrocytes in response to microbial metabolites","volume":"557","author":"Rothhammer","year":"2018","journal-title":"Nature"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"12015","DOI":"10.1038\/ncomms12015","article-title":"Alterations of the human gut microbiome in multiple sclerosis","volume":"7","author":"Jangi","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1016\/j.cell.2019.05.004","article-title":"Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice","volume":"177","author":"Sharon","year":"2019","journal-title":"Cell"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"572","DOI":"10.4049\/jimmunol.1601247","article-title":"Microbiome-Modulated Metabolites at the Interface of Host Immunity","volume":"198","author":"Blacher","year":"2017","journal-title":"J. Immunol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbi.2013.12.015","article-title":"The role of microbiome in central nervous system disorders","volume":"38","author":"Wang","year":"2014","journal-title":"Brain Behav. Immun."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1016\/j.mehy.2004.07.041","article-title":"Hypothesis: A motor neuron toxin produced by a clostridial species residing in gut causes ALS","volume":"64","author":"Longstreth","year":"2005","journal-title":"Med. Hypotheses"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.neurobiolaging.2017.09.023","article-title":"The fecal microbiome of ALS patients","volume":"61","author":"Brenner","year":"2018","journal-title":"Neurobiol. Aging"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"13443","DOI":"10.14814\/phy2.13443","article-title":"Gut inflammation and dysbiosis in human motor neuron disease","volume":"5","author":"Rowin","year":"2017","journal-title":"Physiol. Rep."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/nn.3584","article-title":"State of play in amyotrophic lateral sclerosis genetics","volume":"17","author":"Renton","year":"2014","journal-title":"Nat. Neurosci."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s00401-012-1029-x","article-title":"The genetics and neuropathology of frontotemporal lobar degeneration","volume":"124","author":"Sieben","year":"2012","journal-title":"Acta Neuropathol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"e15","DOI":"10.1016\/j.neurobiolaging.2011.04.004","article-title":"SOD1 G93D sporadic amyotrophic lateral sclerosis (SALS) patient with rapid progression and concomitant novel ANG variant","volume":"32","author":"Luigetti","year":"2011","journal-title":"Neurobiol. Aging"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1136\/jnnp-2012-302219","article-title":"ALS\/FTD phenotype in two Sardinian families carrying both C9ORF72 and TARDBP mutations","volume":"83","author":"Restagno","year":"2012","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"3776","DOI":"10.1093\/hmg\/dds199","article-title":"Evidence for an oligogenic basis of amyotrophic lateral sclerosis","volume":"21","author":"Hennekam","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"024125","DOI":"10.1101\/cshperspect.a024125","article-title":"Genetics of Amyotrophic Lateral Sclerosis","volume":"8","author":"Ghasemi","year":"2018","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1093\/brain\/awr361","article-title":"Frontotemporal dementia with the C9ORF72 hexanucleotide repeat expansion: Clinical, neuroanatomical and neuropathological features","volume":"135","author":"Mahoney","year":"2012","journal-title":"Brain"},{"key":"ref_129","first-page":"266","article-title":"ALS-associated missense and nonsense TBK1 mutations can both cause loss of kinase function","volume":"71","author":"Topp","year":"2018","journal-title":"Neurobiol. Aging"},{"key":"ref_130","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_131","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_132","doi-asserted-by":"crossref","first-page":"E974","DOI":"10.1002\/humu.21100","article-title":"Mutation within TARDBP leads to frontotemporal dementia without motor neuron disease","volume":"30","author":"Borroni","year":"2009","journal-title":"Hum. Mutat."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/nan.12063","article-title":"TARDBP mutation p.Ile383Val associated with semantic dementia and complex proteinopathy","volume":"402","author":"Gelpi","year":"2014","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_134","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_135","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/ng1742","article-title":"ANG mutations segregate with familial and \u2019sporadic\u2019 amyotrophic lateral sclerosis","volume":"38","author":"Greenway","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/nature08971","article-title":"Mutations of optineurin in amyotrophic lateral sclerosis","volume":"465","author":"Maruyama","year":"2010","journal-title":"Nature"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/S1474-4422(11)70261-7","article-title":"A C9 or f72 promoter repeat expansion in a Flanders-Belgian cohortwith disorders of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum: A gene identification study","volume":"11","author":"Gijselinck","year":"2012","journal-title":"Lancet Neurol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1212\/01.wnl.0000299187.90432.3f","article-title":"Prevalence of SOD1 mutations in the Italian ALS population","volume":"70","author":"Traynor","year":"2008","journal-title":"Neurology"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1007\/s00415-005-0742-y","article-title":"SOD1 mutations in amyotrophic lateral sclerosis. Results from a multicenter Italian study","volume":"252","author":"Battistini","year":"2005","journal-title":"J. Neurol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1002\/ana.410410212","article-title":"Epidemiology of mutations in superoxide dismutase in amyotrophic lateral sclerosis","volume":"41","author":"Cudkowicz","year":"1997","journal-title":"Ann. Neurol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1002\/humu.22157","article-title":"ALSoD: A user-friendly online bioinformatics tool for amyotrophic lateral sclerosis genetics","volume":"33","author":"Abel","year":"2012","journal-title":"Hum. Mutat."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1083\/jcb.200908164","article-title":"Non-cell autonomous toxicity in neurodegenerative disorders: ALS and beyond","volume":"187","author":"Ilieva","year":"2009","journal-title":"J. Cell Biol."},{"key":"ref_143","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_144","doi-asserted-by":"crossref","first-page":"4147","DOI":"10.1523\/JNEUROSCI.5461-05.2006","article-title":"Overloading of stable and exclusion of unstable human superoxide dismutase-1 variants in mitochondria of murine amyotrophic lateral sclerosis models","volume":"26","author":"Bergemalm","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"7142","DOI":"10.1073\/pnas.0602046103","article-title":"Conversion to the amyotrophic lateral sclerosis phenotype is associated with intermolecular linked insoluble aggregates of SOD1 in mitochondria","volume":"103","author":"Deng","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.neuron.2004.06.016","article-title":"Toxicity of familial ALS-linked SOD1 mutants from selective recruitment to spinal mitochondria","volume":"43","author":"Liu","year":"2004","journal-title":"Neuron"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s40478-016-0313-8","article-title":"ALS-linked misfolded SOD1 species have divergent impacts on mitochondria","volume":"4","author":"Pickles","year":"2016","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.neuron.2010.07.019","article-title":"Misfolded mutant SOD1 directly inhibits VDAC1 conductance in a mouse model of inherited ALS","volume":"67","author":"Israelson","year":"2010","journal-title":"Neuron"},{"key":"ref_149","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_150","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1136\/jnnp-2016-313521","article-title":"Defining SOD1 ALS natural history to guide therapeutic clinical trial design","volume":"88","author":"Bali","year":"2017","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1159\/000070564","article-title":"A4T mutation in the SOD1 gene causing familial amyotrophic lateral sclerosis","volume":"22","author":"Aksoy","year":"2003","journal-title":"Neuroepidemiology"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1001\/archneur.63.2.262","article-title":"The G93C mutation in superoxide dismutase 1: Clinicopathologic phenotype and prognosis","volume":"63","author":"Vanopdenbosch","year":"2006","journal-title":"Arch. Neurol."},{"key":"ref_153","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_154","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1093\/hmg\/ddp303","article-title":"Mutations in TDP-43 link glycine-rich domain functions to amyotrophic lateral sclerosis","volume":"18","author":"Pesiridis","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_155","first-page":"1081","article-title":"Cytoplasmic inclusions of TDP-43 in neurodegenerative diseases: A potential role for caspases","volume":"24","author":"Rohn","year":"2009","journal-title":"Histol. Histopathol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1021\/pr901076y","article-title":"Global analysis of TDP-43 interacting proteins reveals strong association with RNA splicing and translation machinery","volume":"9","author":"Freibaum","year":"2010","journal-title":"J. Proteome Res."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1111\/j.1468-1331.2008.02195.x","article-title":"ALS and FTLD: Two faces of TDP-43 proteinopathy","volume":"15","author":"Liscic","year":"2008","journal-title":"Eur. J. Neurol."},{"key":"ref_158","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_159","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1212\/01.wnl.0000231510.89311.8b","article-title":"ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B)","volume":"67","author":"Parkinson","year":"2006","journal-title":"Neurology"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1002\/ana.21612","article-title":"TARDBP mutations in motoneuron disease with frontotemporal lobar degeneration","volume":"65","author":"Benajiba","year":"2009","journal-title":"Ann. Neurol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.lfs.2017.12.016","article-title":"New insights into the gene expression associated to amyotrophic lateral sclerosis","volume":"193","year":"2018","journal-title":"Life Sci."},{"key":"ref_162","first-page":"252","article-title":"Current knowledge and recent insights into the genetic basis of amyotrophic lateral sclerosis","volume":"30","author":"Volk","year":"2018","journal-title":"Med. Genet."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"6480","DOI":"10.1007\/s12035-017-0856-0","article-title":"Causative Genes in Amyotrophic Lateral Sclerosis and Protein Degradation Pathways: A Link to Neurodegeneration","volume":"55","author":"Maurel","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"6374","DOI":"10.1523\/JNEUROSCI.20-17-06374.2000","article-title":"KIF5C, a novel neuronal kinesin enriched in motor neurons","volume":"20","author":"Kanai","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/1750-1326-5-52","article-title":"A hereditary spastic paraplegia mutation in kinesin-1A\/KIF5A disrupts neurofilament transport","volume":"15","author":"Wang","year":"2010","journal-title":"Mol. Neurodegener."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1083\/jcb.200301026","article-title":"Abnormal neurofilament transport caused by targeted disruption of neuronal kinesin heavy chain KIF5A","volume":"161","author":"Xia","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1093\/hmg\/8.2.157","article-title":"Deletions of the heavy neurofilament subunit tail in amyotrophic lateral sclerosis","volume":"8","author":"Andersen","year":"1999","journal-title":"Hum. Mol. Genet."},{"key":"ref_168","first-page":"1094","article-title":"Axonal transport and neurodegenerative disease","volume":"762","author":"Holzbaur","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1038\/s41467-017-00911-y","article-title":"HDAC6 inhibition reverses axonal transport defects in motor neurons derived from FUS-ALS patients","volume":"8","author":"Guo","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.brainres.2014.09.065","article-title":"Exploring new pathways of neurodegeneration in ALS: The role of mitochondria quality control","volume":"1607","author":"Alomo","year":"2015","journal-title":"Brain Res."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"132933","DOI":"10.1016\/j.neulet.2017.06.052","article-title":"The role of mitochondria in amyotrophic lateral sclerosis","volume":"710","author":"Smith","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/ni921","article-title":"IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway","volume":"4","author":"Fitzgerald","year":"2003","journal-title":"Nat. Immunol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1038\/ni.1800","article-title":"The TBK1 adaptor and autophagy receptor NDP52 restricts the proliferation of ubiquitin-coated bacteria","volume":"10","author":"Thurston","year":"2009","journal-title":"Nat. Immunol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.immuni.2012.04.015","article-title":"TBK-1 promotes autophagy-mediated antimicrobial defense by controlling autophagosome maturation","volume":"37","author":"Pilli","year":"2012","journal-title":"Immunity"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1038\/cr.2008.273","article-title":"The IKK-related kinases: From innate immunity to oncogenesis","volume":"18","author":"Meloche","year":"2008","journal-title":"Cell Res."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s00401-015-1436-x","article-title":"Whole-genome sequencing reveals important role for TBK1 and OPTN mutations in frontotemporal lobar degeneration without motor neuron disease","volume":"130","author":"Pottier","year":"2015","journal-title":"Acta Neuropathol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"5534","DOI":"10.1007\/s12035-016-0099-5","article-title":"Mitochondrial CHCHD-Containing Proteins: Physiologic Functions and Link with Neurodegenerative Diseases","volume":"54","author":"Zhou","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"e311","DOI":"10.1093\/brain\/awu265","article-title":"Mutations in the CHCHD10 gene are a common cause of familial amyotrophic lateral sclerosis","volume":"137","author":"Johnson","year":"2014","journal-title":"Brain"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"e310","DOI":"10.1093\/brain\/awu228","article-title":"Reply: Two novel mutations in conserved codons indicate that CHCHD10 is a gene associated with motor neuron disease","volume":"137","author":"Bannwarth","year":"2014","journal-title":"Brain"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"e309","DOI":"10.1093\/brain\/awu227","article-title":"Two novel mutations in conserved codons indicate that CHCHD10 is a gene associated with motor neuron disease","volume":"137","author":"Andersen","year":"2014","journal-title":"Brain"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10048-014-0421-1","article-title":"Mutation in the novel nuclear-encoded mitochondrial protein CHCHD10 in a family with autosomal dominant mitochondrial myopathy","volume":"16","author":"Fecto","year":"2015","journal-title":"Neurogenetics"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1002\/ana.24319","article-title":"Late onset spinal motor neuronopathy is caused by mutation in CHCHD10","volume":"77","author":"Jokela","year":"2015","journal-title":"Ann. Neurol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/ng1332","article-title":"Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein","volume":"36","author":"Watts","year":"2004","journal-title":"Nat. Genet."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.ajhg.2009.03.006","article-title":"Autosomal-dominant distal myopathy associated with a recurrent missense mutation in the gene encoding the nuclear matrix protein, matrin 3","volume":"84","author":"Senderek","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"15558","DOI":"10.1038\/ncomms15558","article-title":"Loss of function CHCHD10 mutations in cytoplasmic TDP-43 accumulation and synaptic integrity","volume":"8","author":"Woo","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_186","doi-asserted-by":"crossref","unstructured":"Salton, M., Elkon, R., Borodina, T., Davydov, A., Yaspo, M.-L., Halperin, E., and Shiloh, Y. (2011). Matrin 3 binds and stabilizes mRNA. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023882"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"653","DOI":"10.15252\/embj.201489852","article-title":"Nuclear matrix protein Matrin3 regulates alternative splicing and forms overlapping regulatory networks with PTB","volume":"34","author":"Coelho","year":"2015","journal-title":"EMBO J."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"2882","DOI":"10.1016\/j.neurobiolaging.2014.07.012","article-title":"Genetic architecture of ALS in Sardinia","volume":"35","author":"Borghero","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"530","DOI":"10.3109\/21678421.2015.1058397","article-title":"A novel Arg147Trp MATR3 missense mutation in a slowly progressive ALS Italian patient","volume":"16","author":"Origone","year":"2015","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.neurobiolaging.2015.02.008","article-title":"Mutational analysis of MATR3 in Taiwanese patients with amyotrophic lateral sclerosis","volume":"36","author":"Lin","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"18999","DOI":"10.3390\/ijms140918999","article-title":"hnRNP A1: The Swiss army knife of gene expression","volume":"14","author":"Paz","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/nature11922","article-title":"Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS","volume":"495","author":"Kim","year":"2013","journal-title":"Nature"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.jmb.2016.12.011","article-title":"Methylarginines within the RGG-Motif Region of hnRNP A1 Affect Its IRES Trans-Acting Factor Activity and Are Required for hnRNP A1 Stress Granule Localization and Formation","volume":"429","author":"Wall","year":"2017","journal-title":"J. Mol. Biol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1074\/mcp.M500255-MCP200","article-title":"Characterization of an RNA granule from developing brain","volume":"5","author":"Elvira","year":"2006","journal-title":"Mol. Cell Proteom."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"5744","DOI":"10.1128\/MCB.00224-06","article-title":"hnRNP A1 relocalization to the stress granules reflects a role in the stress response","volume":"26","author":"Guil","year":"2006","journal-title":"Mol. Cell Biol."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1093\/hmg\/ddr021","article-title":"TAR DNA-binding protein 43 (TDP-43) regulates stress granule dynamics via differential regulation of G3BP and TIA-1","volume":"20","author":"Aulas","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1212\/WNL.0000000000001862","article-title":"Multisystem proteinopathy: Intersecting genetics in muscle, bone, and brain degeneration","volume":"85","author":"Taylor","year":"2015","journal-title":"Neurology"},{"key":"ref_198","first-page":"572","article-title":"Welander distal myopathy caused by an ancient founder mutation in TIA1 associated with perturbed splicing","volume":"34","author":"Klar","year":"2013","journal-title":"Hum. Mutat."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.nmd.2016.05.012","article-title":"Distal myopathy with coexisting heterozygous TIA1 and MYH7 Variants","volume":"26","author":"Brand","year":"2016","journal-title":"Neuromuscul. Disord."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1002\/ana.23831","article-title":"Welander distal myopathy is caused by a mutation in the RNA-binding protein TIA1","volume":"73","author":"Hackman","year":"2013","journal-title":"Ann. Neurol."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1016\/j.febslet.2008.03.036","article-title":"The mammalian Nek1 kinase is involved in primary cilium formation","volume":"582","author":"Shalom","year":"2008","journal-title":"FEBS Lett."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"257","DOI":"10.4161\/cc.8.2.7551","article-title":"Nek1 regulates cell death and mitochondrial membrane permeability through phosphorylation of VDAC1","volume":"8","author":"Chen","year":"2009","journal-title":"Cell Cycle"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1093\/mutage\/geq026","article-title":"Nek1 silencing slows down DNA repair and blocks DNA damage-induced cell cycle arrest","volume":"25","author":"Pelegrini","year":"2010","journal-title":"Mutagenesis"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1093\/abbs\/gmv076","article-title":"The NEK1 interactor, C21ORF2, is required for efficient DNA damage repair","volume":"47","author":"Fang","year":"2015","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_205","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_206","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.neurobiolaging.2017.08.021","article-title":"NEK1 genetic variability in a Belgian cohort of ALS and ALS-FTD patients","volume":"61","author":"Nguyen","year":"2018","journal-title":"Neurobiol. Aging"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"2274","DOI":"10.1242\/jcs.048975","article-title":"The NIMA-family kinase Nek3 regulates microtubule acetylation in neurons","volume":"122","author":"Chang","year":"2009","journal-title":"J. Cell Sci."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"4301","DOI":"10.1007\/s00018-018-2873-1","article-title":"Dysregulation of a novel miR-1825\/TBCB\/TUBA4A pathway in sporadic and familial ALS","volume":"75","author":"Helferich","year":"2018","journal-title":"Cell Mol. Life Sci."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"594975","DOI":"10.3389\/fncel.2020.594975","article-title":"The Neglected Genes of ALS: Cytoskeletal Dynamics Impact Synaptic Degeneration in ALS","volume":"14","author":"Chaineau","year":"2020","journal-title":"Front. Cell. Neurosci."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nature11280","article-title":"Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis","volume":"488","author":"Wu","year":"2012","journal-title":"Nature"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1007\/s00415-009-0078-0","article-title":"SOD1 and cognitive dysfunction in familial amyotrophic lateral sclerosis","volume":"256","author":"Wicks","year":"2009","journal-title":"J. Neurol."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/j.neurobiolaging.2011.10.029","article-title":"UNC13A is a modifier of survival in amyotrophic lateral sclerosis","volume":"33","author":"Diekstra","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.neurobiolaging.2016.11.010","article-title":"ATXN2 trinucleotide repeat length correlates with risk of ALS","volume":"51","author":"Sproviero","year":"2017","journal-title":"Neurobiol. Aging"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.neurobiolaging.2017.11.011","article-title":"ATXN1 intermediate-length polyglutamine expansions are associated with amyotrophic lateral sclerosis","volume":"64","author":"Lattante","year":"2018","journal-title":"Neurobiol. Aging"},{"key":"ref_215","doi-asserted-by":"crossref","unstructured":"Uyan, \u00d6., \u00d6m\u00fcr, \u00d6., A\u011f\u0131m, Z.S., \u00d6zo\u011fuz, A., Li, H., Parman, Y., Deymeer, F., Oflazer, P., Ko\u00e7, F., and Tan, E. (2013). Genome-wide copy number variation in sporadic amyotrophic lateral sclerosis in the Turkish population: Deletion of EPHA3 is a possible protective factor. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0072381"},{"key":"ref_216","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_217","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1002\/ana.24306","article-title":"Amyotrophic lateral sclerosis onset is influenced by the burden of rare variants in known amyotrophic lateral sclerosis genes","volume":"77","author":"Cady","year":"2015","journal-title":"Ann. Neurol."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.neurobiolaging.2015.11.030","article-title":"Next-generation sequencing of 28 ALS-related genes in a Japanese ALS cohort","volume":"39","author":"Nakamura","year":"2016","journal-title":"Neurobiol. Aging"},{"key":"ref_220","first-page":"06866","article-title":"Evidence for polygenic and oligogenic basis of Australian sporadic amyotrophic lateral sclerosis","volume":"14","author":"Henden","year":"2020","journal-title":"J. Med. Genet."},{"key":"ref_221","doi-asserted-by":"crossref","unstructured":"Vasilopoulou, C., Morris, A.P., Giannakopoulos, G., Duguez, S., and Duddy, W. (2020). What Can Machine Learning Approaches in Genomics Tell Us about the Molecular Basis of Amyotrophic Lateral Sclerosis?. J. Pers. Med., 10.","DOI":"10.3390\/jpm10040247"},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"R65","DOI":"10.1093\/hmg\/ddq162","article-title":"Genetics of neurodegenerative diseases: Insights from high-throughput resequencing","volume":"19","author":"Tsuji","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1007\/s12035-014-8724-7","article-title":"Antisense oligonucleotide therapy for the treatment of C9ORF72 ALS\/FTD diseases","volume":"50","author":"Riboldi","year":"2014","journal-title":"Mol. Neurobiol."},{"key":"ref_224","doi-asserted-by":"crossref","unstructured":"Cappella, M., Ciotti, C., Cohen-Tannoudji, M., and Biferi, M.G. (2019). Gene Therapy for ALS-A Perspective. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184388"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/3\/509\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:35:10Z","timestamp":1760160910000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/3\/509"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,13]]},"references-count":224,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["diagnostics11030509"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics11030509","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,13]]}}}