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dc.contributor.authorJara, Javier H.
dc.contributor.authorGenç, Barış
dc.contributor.authorCox, Gregory
dc.contributor.authorBohn, Martha C.
dc.contributor.authorRoos, Raymond P.
dc.contributor.authorMacklis, Jeffrey Daniel
dc.contributor.authorUlupınar, Emel
dc.contributor.authorHande Ozdinler, P.
dc.date.accessioned2017-04-07T20:01:17Z
dc.date.issued2015
dc.identifierQuick submit: 2015-01-21T08:55:19-05:00
dc.identifier.citationJara, Javier H., Barış Genç, Gregory A. Cox, Martha C. Bohn, Raymond P. Roos, Jeffrey Daniel Macklis, Emel Ulupınar, and P. Hande Ozdinler. 2015. “Corticospinal Motor Neurons Are Susceptible to Increased ER Stress and Display Profound Degeneration in the Absence of UCHL1 Function.” Cerebral Cortex 25, no. 11: 4259-4272.en_US
dc.identifier.issn1047-3211en_US
dc.identifier.issn1460-2199en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:32097109
dc.description.abstractCorticospinal motor neurons (CSMN) receive, integrate, and relay cerebral cortex's input toward spinal targets to initiate and modulate voluntary movement. CSMN degeneration is central for numerous motor neuron disorders and neurodegenerative diseases. Previously, 5 patients with mutations in the ubiquitin carboxy-terminal hydrolase-L1 (UCHL1) gene were reported to have neurodegeneration and motor neuron dysfunction with upper motor neuron involvement. To investigate the role of UCHL1 on CSMN health and stability, we used both in vivo and in vitro approaches, and took advantage of the \(Uchl1^{nm3419}\) \((UCHL1^{−/−})\) mice, which lack all UCHL1 function. We report a unique role of UCHL1 in maintaining CSMN viability and cellular integrity. CSMN show early, selective, progressive, and profound cell loss in the absence of UCHL1. CSMN degeneration, evident even at pre-symptomatic stages by disintegration of the apical dendrite and spine loss, is mediated via increased ER stress. These findings bring a novel understanding to the basis of CSMN vulnerability, and suggest \(UCHL1^{−/−}\) mice as a tool to study CSMN pathology.en_US
dc.description.sponsorshipStem Cell and Regenerative Biologyen_US
dc.language.isoen_USen_US
dc.publisherOxford University Pressen_US
dc.relation.isversionofdoi:10.1093/cercor/bhu318en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pubmed/25596590en_US
dash.licenseMETA_ONLY
dc.subjectAAV2-mediated transductionen_US
dc.subjectapical dendriteen_US
dc.subjectCSMNen_US
dc.subjectER stressen_US
dc.titleCorticospinal Motor Neurons Are Susceptible to Increased ER Stress and Display Profound Degeneration in the Absence of UCHL1 Functionen_US
dc.typeJournal Articleen_US
dc.date.updated2015-01-21T13:55:19Z
dc.description.versionVersion of Recorden_US
dc.rights.holderJavier H. Jara; Barış Genc; Gregory A. Cox; Martha C. Bohn; Raymond P. Roos; Jeffrey D. Macklis; Emel Ulupınar; P. Hande Ozdinler
dc.relation.journalCerebral Cortexen_US
dash.depositing.authorMacklis, Jeffrey Daniel
dash.embargo.until10000-01-01
dc.identifier.doi10.1093/cercor/bhu318*
workflow.legacycommentsMacklis emailed 2016-04-24 MM meta.darken_US
dash.contributor.affiliatedCox, Gregory
dash.contributor.affiliatedMacklis, Jeffrey


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