Corticospinal Motor Neurons Are Susceptible to Increased ER Stress and Display Profound Degeneration in the Absence of UCHL1 Function
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Jara, Javier H.
Genç, Barış
Bohn, Martha C.
Roos, Raymond P.
Ulupınar, Emel
Hande Ozdinler, P.
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https://doi.org/10.1093/cercor/bhu318Metadata
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Jara, 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.Abstract
Corticospinal 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.Other Sources
http://www.ncbi.nlm.nih.gov/pubmed/25596590Citable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:32097109
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Macklis emailed 2016-04-24 MM meta.dark