{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T22:16:26Z","timestamp":1788300986281,"version":"build-2803163510"},"reference-count":34,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T00:00:00Z","timestamp":1785628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP22ek0109603"],"award-info":[{"award-number":["JP22ek0109603"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP24K22094"],"award-info":[{"award-number":["JP24K22094"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP25K02462"],"award-info":[{"award-number":["JP25K02462"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neurobiology of Disease"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1016\/j.nbd.2026.107560","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T06:48:03Z","timestamp":1785826083000},"page":"107560","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Persistent export bias of TDP-43 under native autoregulation links insoluble accumulation to nuclear dysfunction"],"prefix":"10.1016","volume":"228","author":[{"given":"Genri","family":"Toyama","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shingo","family":"Koide","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuma","family":"Yamagishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Washida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryutaro","family":"Hanyu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Onodera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Sugai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.nbd.2026.107560_bb0005","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"10.1016\/j.nbd.2026.107560_bb0010","doi-asserted-by":"crossref","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":"10.1016\/j.nbd.2026.107560_bb0015","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":"10.1016\/j.nbd.2026.107560_bb0020","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/s41586-021-04199-3","article-title":"Structure of pathological TDP-43 filaments from ALS with FTLD","volume":"601","author":"Arseni","year":"2022","journal-title":"Nature"},{"key":"10.1016\/j.nbd.2026.107560_bb0025","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1101\/gad.194829.112","article-title":"Autoregulation of TDP-43 mRNA levels involves interplay between transcription, splicing, and alternative polyA site selection","volume":"26","author":"Avenda\u00f1o-V\u00e1zquez","year":"2012","journal-title":"Genes Dev."},{"key":"10.1016\/j.nbd.2026.107560_bb0030","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":"10.1016\/j.nbd.2026.107560_bb0035","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":"10.1016\/j.nbd.2026.107560_bb0040","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":"10.1016\/j.nbd.2026.107560_bb0045","doi-asserted-by":"crossref","first-page":"4167","DOI":"10.1111\/febs.70429","article-title":"Concentration-dependent cytoplasmic phase separation of TDP-43 drives aggregation and proteinopathy","volume":"293","author":"Combe","year":"2026","journal-title":"FEBS J."},{"key":"10.1016\/j.nbd.2026.107560_bb0050","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.neuron.2019.02.038","article-title":"Cytoplasmic TDP-43 de-mixing independent of stress granules drives inhibition of nuclear import, loss of nuclear TDP-43, and cell death","volume":"102","author":"Gasset-Rosa","year":"2019","journal-title":"Neuron"},{"key":"10.1016\/j.nbd.2026.107560_bb0055","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":"10.1016\/j.nbd.2026.107560_bb0060","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":"10.1016\/j.nbd.2026.107560_bb0065","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1002\/1873-3468.70198","article-title":"Quantifying subpercent nuclear TDP-43 loss in cells and ALS cortex using junction-specific cryptic exon RT-qPCR","volume":"600","author":"Koide","year":"2026","journal-title":"FEBS Lett."},{"key":"10.1016\/j.nbd.2026.107560_bb0070","doi-asserted-by":"crossref","first-page":"5820","DOI":"10.1093\/nar\/gkw499","article-title":"Increased cytoplasmic TARDBP mRNA in affected spinal motor neurons in ALS caused by abnormal autoregulation of TDP-43","volume":"44","author":"Koyama","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.nbd.2026.107560_bb0075","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/nrn3121","article-title":"Gains or losses: molecular mechanisms of TDP43-mediated neurodegeneration","volume":"13","author":"Lee","year":"2012","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.nbd.2026.107560_bb0080","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":"10.1016\/j.nbd.2026.107560_bb0085","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3003662","article-title":"A quantitative cell-based reporter links TDP-43 aggregation and dysfunction to define pathogenic mechanisms","volume":"24","author":"Mamede","year":"2026","journal-title":"PLoS Biol."},{"key":"10.1016\/j.nbd.2026.107560_bb0090","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/s41593-018-0293-z","article-title":"Premature polyadenylation-mediated loss of stathmin-2 is a hallmark of TDP-43-dependent neurodegeneration","volume":"22","author":"Melamed","year":"2019","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.nbd.2026.107560_bb0095","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s00401-008-0396-9","article-title":"Maturation process of TDP-43-positive neuronal cytoplasmic inclusions in amyotrophic lateral sclerosis with and without dementia","volume":"116","author":"Mori","year":"2008","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.nbd.2026.107560_bb0100","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":"10.1016\/j.nbd.2026.107560_bb0105","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1002\/pro.3943","article-title":"UCSF ChimeraX: structure visualization for researchers, educators, and developers","volume":"30","author":"Pettersen","year":"2021","journal-title":"Protein Sci."},{"key":"10.1016\/j.nbd.2026.107560_bb0110","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/nn.2779","article-title":"Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43","volume":"14","author":"Polymenidou","year":"2011","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.nbd.2026.107560_bb0115","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1093\/brain\/aww197","article-title":"Nuclear trafficking in amyotrophic lateral sclerosis and frontotemporal lobar degeneration","volume":"140","author":"Prpar Mihevc","year":"2017","journal-title":"Brain"},{"key":"10.1016\/j.nbd.2026.107560_bb0120","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0043120","article-title":"Alteration of POLDIP3 splicing associated with loss of function of TDP-43 in tissues affected with ALS","volume":"7","author":"Shiga","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.nbd.2026.107560_bb0125","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":"10.1016\/j.nbd.2026.107560_bb0130","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2018.00028","article-title":"Robustness and vulnerability of the autoregulatory system that maintains nuclear TDP-43 levels: a trade-off hypothesis for ALS pathology based on in silico data","volume":"12","author":"Sugai","year":"2018","journal-title":"Front. Neurosci."},{"key":"10.1016\/j.nbd.2026.107560_bb0135","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":"10.1016\/j.nbd.2026.107560_bb0140","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":"10.1016\/j.nbd.2026.107560_bb0145","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1007\/s00401-015-1460-x","article-title":"Functional recovery in new mouse models of ALS\/FTLD after clearance of pathological cytoplasmic TDP-43","volume":"130","author":"Walker","year":"2015","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.nbd.2026.107560_bb0150","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/0092-8674(95)90435-2","article-title":"Identification of a signal for rapid export of proteins from the nucleus","volume":"82","author":"Wen","year":"1995","journal-title":"Cell"},{"key":"10.1016\/j.nbd.2026.107560_bb0155","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":"10.1016\/j.nbd.2026.107560_bb0160","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1126\/science.aad2033","article-title":"Cytoplasmic protein aggregates interfere with nucleocytoplasmic transport of protein and RNA","volume":"351","author":"Woerner","year":"2016","journal-title":"Science"},{"key":"10.1016\/j.nbd.2026.107560_bb0165","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1016\/j.cell.2018.03.025","article-title":"Stress granule assembly disrupts nucleocytoplasmic transport","volume":"173","author":"Zhang","year":"2018","journal-title":"Cell"},{"key":"10.1016\/j.nbd.2026.107560_bb0170","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."}],"container-title":["Neurobiology of Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0969996126003050?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0969996126003050?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T22:00:18Z","timestamp":1788300018000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0969996126003050"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":34,"alternative-id":["S0969996126003050"],"URL":"https:\/\/doi.org\/10.1016\/j.nbd.2026.107560","relation":{},"ISSN":["0969-9961"],"issn-type":[{"value":"0969-9961","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Persistent export bias of TDP-43 under native autoregulation links insoluble accumulation to nuclear dysfunction","name":"articletitle","label":"Article Title"},{"value":"Neurobiology of Disease","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.nbd.2026.107560","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"107560"}}