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dc.contributor.authorSteele, Andrew D.
dc.contributor.authorLindquist, Susan
dc.contributor.authorJackson, Walker S.
dc.contributor.authorAuluck, Pavan K.
dc.contributor.authorZhu, Chunni
dc.contributor.authorZhou, Zhipeng
dc.contributor.authorMoskowitz, Michael A.
dc.contributor.authorChesselet, Marie-Francoise
dc.date.accessioned2011-11-03T17:34:41Z
dc.date.available2011-11-03T17:34:41Z
dc.date.issued2009-01
dc.identifier.issn1933-6896
dc.identifier.issn1933-690X
dc.identifier.urihttp://hdl.handle.net/1721.1/66911
dc.description.abstractAlthough it has been known for more than twenty years that an aberrant conformation of the prion protein (PrP) is the causative agent in prion diseases, the role of PrP in normal biology is undetermined. Numerous studies have suggested a protective function for PrP, including protection from ischemic and excitotoxic lesions and several apoptotic insults. On the other hand, many observations have suggested the contrary, linking changes in PrP localization or domain structure—independent of infectious prion conformation—to severe neuronal damage. Surprisingly, a recent report suggests that PrP is a receptor for toxic oligomeric species of a-β, a pathogenic fragment of the amyloid precursor protein, and likely contributes to disease pathogenesis of Alzheimer’s disease. We sought to access the role of PrP in diverse neurological disorders. First, we confirmed that PrP confers protection against ischemic damage using an acute stroke model, a well characterized association. After ischemic insult, PrP knockouts had dramatically increased infarct volumes and decreased behavioral performance compared to controls. To examine the potential of PrP’s neuroprotective or neurotoxic properties in the context of other pathologies, we deleted PrP from several transgenic models of neurodegenerative disease. Deletion of PrP did not substantially alter the disease phenotypes of mouse models of Parkinson’s disease or tauopathy. Deletion of PrP in one of two Huntington’s disease models tested, R6/2, modestly slowed motor deterioration as measured on an accelerating rotarod but otherwise did not alter other major features of the disease. Finally, transgenic overexpression of PrP did not exacerbate the Huntington’s motor phenotype. These results suggest that PrP has a context-dependent neuroprotective function and does not broadly contribute to the disease models tested herein.en_US
dc.description.sponsorshipEllison Medical Foundationen_US
dc.description.sponsorshipWhitaker Health Sciences Fund Fellowshipen_US
dc.language.isoen_US
dc.publisherLandes Bioscienceen_US
dc.relation.isversionofhttp://dx.doi.org/10.4161/pri.3.4.10135en_US
dc.rightsCreative Commons Attribution-Noncommercial-Share Alike 3.0en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/en_US
dc.sourceLindquisten_US
dc.titleContext Dependent Neuroprotective Properties of Prion Protein (Prp)en_US
dc.typeArticleen_US
dc.identifier.citationSteele, Andrew D. et al. “Context dependent neuroprotective properties of prion protein (PrP).” Prion 3 (2009): 240-249. Web. 3 Nov. 2011. © 2009 Landes Bioscienceen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.approverLindquist, Susan
dc.contributor.mitauthorSteele, Andrew D.
dc.contributor.mitauthorLindquist, Susan
dc.contributor.mitauthorJackson, Walker S.
dc.contributor.mitauthorAuluck, Pavan K.
dc.relation.journalPrionen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsSteele, Andrew D.; Zhou, Zhipeng; Jackson, Walker S.; Zhu, Chunni; Auluck, Pavan; Moskowitz, Michael A.; Chesselet, Marie-Francoise; Lindquist, Susanen
dc.identifier.orcidhttps://orcid.org/0000-0003-1307-882X
mit.licenseOPEN_ACCESS_POLICYen_US
mit.metadata.statusComplete


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