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dc.contributor.authorChou, Ching-Chieh
dc.contributor.authorZhang, Yi
dc.contributor.authorUmoh, Mfon E.
dc.contributor.authorVaughan, Spencer W.
dc.contributor.authorLorenzini, Ileana
dc.contributor.authorLiu, Feilin
dc.contributor.authorSayegh, Melissa
dc.contributor.authorDonlin-Asp, Paul G.
dc.contributor.authorChen, Yu Han
dc.contributor.authorDuong, Duc M.
dc.contributor.authorSeyfried, Nicholas T.
dc.contributor.authorPowers, Maureen A.
dc.contributor.authorKukar, Thomas
dc.contributor.authorHales, Chadwick M.
dc.contributor.authorGearing, Marla
dc.contributor.authorCairns, Nigel J.
dc.contributor.authorBoylan, Kevin B.
dc.contributor.authorDickson, Dennis W.
dc.contributor.authorRademakers, Rosa
dc.contributor.authorZhang, Yong-Jie
dc.contributor.authorPetrucelli, Leonard
dc.contributor.authorSattler, Rita
dc.contributor.authorZarnescu, Daniela C.
dc.contributor.authorGlass, Jonathan D.
dc.contributor.authorRossoll, Wilfried
dc.date.accessioned2018-06-14T18:47:32Z
dc.date.available2018-06-14T18:47:32Z
dc.date.issued2018-02
dc.identifier.citationChou, C. C., Zhang, Y., Umoh, M. E., Vaughan, S. W., Lorenzini, I., Liu, F., ... & Seyfried, N. T. (2018). TDP-43 pathology disrupts nuclear pore complexes and nucleocytoplasmic transport in ALS/FTD. Nature neuroscience, 21, pp 228–239, https://doi.org/10.1038/s41593-017-0047-3en_US
dc.identifier.issn1097-6256
dc.identifier.issn1546-1726
dc.identifier.pmid29311743
dc.identifier.doi10.1038/s41593-017-0047-3
dc.identifier.urihttp://hdl.handle.net/10150/627973
dc.description.abstractThe cytoplasmic mislocalization and aggregation of TAR DNA-binding protein-43 (TDP-43) is a common histopathological hallmark of the amyotrophic lateral sclerosis and frontotemporal dementia disease spectrum (ALS/FTD). However, the composition of aggregates and their contribution to the disease process remain unknown. Here we used proximity-dependent biotin identification (BioID) to interrogate the interactome of detergent-insoluble TDP-43 aggregates and found them enriched for components of the nuclear pore complex and nucleocytoplasmic transport machinery. Aggregated and disease-linked mutant TDP-43 triggered the sequestration and/or mislocalization of nucleoporins and transport factors, and interfered with nuclear protein import and RNA export in mouse primary cortical neurons, human fibroblasts and induced pluripotent stem cell-derived neurons. Nuclear pore pathology is present in brain tissue in cases of sporadic ALS and those involving genetic mutations in TARDBP and C9orf72. Our data strongly implicate TDP-43-mediated nucleocytoplasmic transport defects as a common disease mechanism in ALS/FTD.en_US
dc.description.sponsorshipALS Association [17-IIP-353, 16-IIP-278]; Emory Medicine Catalyst Funding Program; Muscular Dystrophy Association [MDA348086]; NIH [K08-NS087121, P30-NS055077, AG025688, R01-NS091299, R35-NS097261, R01-NS085207, R01NS091749, R01-NS093362, R01-AG053960]; The Bluefield Project to Cure FTD; Alzheimers Drug Discovery Foundation; Alzheimers Association (ALZ); Alzheimers Research UK (ARUK); The Michael J. Fox Foundation for Parkinsons Research (MJFF); Weston Brain Institute Biomarkers Across Neurodegenerative Diseases Grant [11060]; UBRP; UA Provosts Office; ARCS Fellowship Roche Foundation Awarden_US
dc.language.isoenen_US
dc.publisherNATURE PUBLISHING GROUPen_US
dc.relation.urlhttp://www.nature.com/articles/s41593-017-0047-3en_US
dc.rightsCopyright © 2018, Springer Nature.en_US
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.titleTDP-43 pathology disrupts nuclear pore complexes and nucleocytoplasmic transport in ALS/FTDen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Dept Mol & Cellular Biolen_US
dc.identifier.journalNATURE NEUROSCIENCEen_US
dc.description.note6 month embargo; published online: 08 January 2018en_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal accepted manuscripten_US
dc.source.journaltitleNature Neuroscience
dc.source.volume21
dc.source.issue2
dc.source.beginpage228
dc.source.endpage239


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