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dc.contributor.authorSeo, Jinsoo
dc.contributor.authorZhou, Ying
dc.contributor.authorRudenko, Andrii
dc.contributor.authorCho, Sukhee
dc.contributor.authorOta, Kristie
dc.contributor.authorPark, Christine
dc.contributor.authorPatzke, Holger
dc.contributor.authorMadabhushi, Ram
dc.contributor.authorPan, Ling
dc.contributor.authorGuan, Ji-Song
dc.contributor.authorDelalle, Ivana
dc.contributor.authorTsai, Li-Huei
dc.contributor.authorGiusti-Rodriguez, Paola
dc.contributor.authorMungenast, Alison
dc.date.accessioned2016-05-16T13:40:35Z
dc.date.available2016-05-16T13:40:35Z
dc.date.issued2014-04
dc.date.submitted2013-11
dc.identifier.issn00928674
dc.identifier.issn1097-4172
dc.identifier.urihttp://hdl.handle.net/1721.1/102509
dc.description.abstractCyclin-dependent kinase 5 regulates numerous neuronal functions with its activator, p35. Under neurotoxic conditions, p35 undergoes proteolytic cleavage to liberate p25, which has been implicated in various neurodegenerative diseases. Here, we show that p25 is generated following neuronal activity under physiological conditions in a GluN2B- and CaMKIIα-dependent manner. Moreover, we developed a knockin mouse model in which endogenous p35 is replaced with a calpain-resistant mutant p35 (Δp35KI) to prevent p25 generation. The Δp35KI mice exhibit impaired long-term depression and defective memory extinction, likely mediated through persistent GluA1 phosphorylation at Ser845. Finally, crossing the Δp35KI mice with the 5XFAD mouse model of Alzheimer’s disease (AD) resulted in an amelioration of β-amyloid (Aβ)-induced synaptic depression and cognitive impairment. Together, these results reveal a physiological role of p25 production in synaptic plasticity and memory and provide new insights into the function of p25 in Aβ-associated neurotoxicity and AD-like pathology.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant R01 NS051874)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant F31GM80055-03)en_US
dc.description.sponsorshipHoward Hughes Medical Instituteen_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.cell.2014.01.065en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourcePMCen_US
dc.titleActivity-Dependent p25 Generation Regulates Synaptic Plasticity and Aβ-Induced Cognitive Impairmenten_US
dc.typeArticleen_US
dc.identifier.citationSeo, Jinsoo, Paola Giusti-Rodríguez, Ying Zhou, Andrii Rudenko, Sukhee Cho, Kristie T. Ota, Christine Park, et al. “Activity-Dependent P25 Generation Regulates Synaptic Plasticity and Aβ-Induced Cognitive Impairment.” Cell 157, no. 2 (April 2014): 486–498.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciencesen_US
dc.contributor.departmentPicower Institute for Learning and Memoryen_US
dc.contributor.mitauthorSeo, Jinsooen_US
dc.contributor.mitauthorGiusti-Rodriguez, Paolaen_US
dc.contributor.mitauthorZhou, Yingen_US
dc.contributor.mitauthorRudenko, Andriien_US
dc.contributor.mitauthorCho, Sukheeen_US
dc.contributor.mitauthorOta, Kristie T.en_US
dc.contributor.mitauthorPark, Christineen_US
dc.contributor.mitauthorPatzke, Holgeren_US
dc.contributor.mitauthorMadabhushi, Ramen_US
dc.contributor.mitauthorPan, Lingen_US
dc.contributor.mitauthorMungenast, Alisonen_US
dc.contributor.mitauthorGuan, Ji-Songen_US
dc.contributor.mitauthorTsai, Li-Hueien_US
dc.relation.journalCellen_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.orderedauthorsSeo, Jinsoo; Giusti-Rodríguez, Paola; Zhou, Ying; Rudenko, Andrii; Cho, Sukhee; Ota, Kristie T.; Park, Christine; Patzke, Holger; Madabhushi, Ram; Pan, Ling; Mungenast, Alison E.; Guan, Ji-Song; Delalle, Ivana; Tsai, Li-Hueien_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0001-9947-9071
dc.identifier.orcidhttps://orcid.org/0000-0003-1262-0592
dspace.mitauthor.errortrue
mit.licensePUBLISHER_CCen_US


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