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dc.contributor.authorSeo, Hyemyung
dc.contributor.authorSonntag, Kai-Christian
dc.contributor.authorKim, Woori
dc.contributor.authorCattaneo, Elena
dc.contributor.authorIsacson, Ole Stefan
dc.date.accessioned2011-06-14T18:31:27Z
dc.date.issued2007
dc.identifier.citationSeo, Hyemyung, Kai-Christian Sonntag, Woori Kim, Elena Cattaneo, and Ole Isacson. 2007. Proteasome activator enhances survival of Huntington's Disease neuronal model cells. PLoS ONE 2(2): e238.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4911699
dc.description.abstractIn patients with Huntington's disease (HD), the proteolytic activity of the ubiquitin proteasome system (UPS) is reduced in the brain and other tissues. The pathological hallmark of HD is the intraneuronal nuclear protein aggregates of mutant huntingtin. We determined how to enhance UPS function and influence catalytic protein degradation and cell survival in HD. Proteasome activators involved in either the ubiquitinated or the non-ubiquitinated proteolysis were overexpressed in HD patients' skin fibroblasts or mutant huntingtin-expressing striatal neurons. Following compromise of the UPS, overexpression of the proteasome activator subunit PA28γ, but not subunit S5a, recovered proteasome function in the HD cells. PA28γ also improved cell viability in mutant huntingtin-expressing striatal neurons exposed to pathological stressors, such as the excitotoxin quinolinic acid and the reversible proteasome inhibitor MG132. These results demonstrate the specific functional enhancements of the UPS that can provide neuroprotection in HD cells.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0000238en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1800909/pdf/en_US
dash.licenseLAA
dc.subjectneuroscienceen_US
dc.titleProteasome Activator Enhances Survival of Huntington's Disease Neuronal Model Cellsen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorSonntag, Kai-Christian
dc.date.available2011-06-14T18:31:27Z
dash.affiliation.otherHMS^Psychiatry-McLean Hospitalen_US
dash.affiliation.otherHMS^Neurology-Massachusetts General Hospitalen_US
dc.identifier.doi10.1371/journal.pone.0000238*
dash.contributor.affiliatedSeo, Hyemyung
dash.contributor.affiliatedSonntag, Kai-Christian
dash.contributor.affiliatedIsacson, Ole


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