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dc.contributor.authorGräff, Johannes
dc.contributor.authorRei, Damien
dc.contributor.authorGuan, Ji-Song
dc.contributor.authorWang, Wen-Yuan
dc.contributor.authorSeo, Jinsoo
dc.contributor.authorFass, Daniel M.
dc.contributor.authorKao, Patricia F.
dc.contributor.authorKahn, Martin
dc.contributor.authorSu, Susan C.
dc.contributor.authorJoseph, Nadine
dc.contributor.authorDelalle, Ivana
dc.contributor.authorTsai, Li-Huei
dc.contributor.authorHennig, Krista M.
dc.contributor.authorNieland, Thomas
dc.contributor.authorSamiei, Alireza
dc.contributor.authorHaggarty, Stephen John
dc.date.accessioned2013-04-23T13:14:42Z
dc.date.issued2012
dc.identifier.citationGräff, Johannes, Damien Rei, Ji-Song Guan, Wen-Yuan Wang, Jinsoo Seo, Krista M. Hennig, Thomas Nieland, et al. 2012. An epigenetic blockade of cognitive functions in the neurodegenerating brain. Nature 483(7388): 222-226.en_US
dc.identifier.issn0028-0836en_US
dc.identifier.issn1476-4687en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10579390
dc.description.abstractCognitive decline is a debilitating feature of most neurodegenerative diseases of the central nervous system, including Alzheimer’s disease. The causes leading to such impairment are only poorly understood and effective treatments are slow to emerge. Here we show that cognitive capacities in the neurodegenerating brain are constrained by an epigenetic blockade of gene transcription that is potentially reversible. This blockade is mediated by histone deacetylase 2, which is increased by Alzheimer’s-disease-related neurotoxic insults in vitro, in two mouse models of neurodegeneration and in patients with Alzheimer’s disease. Histone deacetylase 2 associates with and reduces the histone acetylation of genes important for learning and memory, which show a concomitant decrease in expression. Importantly, reversing the build-up of histone deacetylase 2 by short-hairpin-RNA-mediated knockdown unlocks the repression of these genes, reinstates structural and synaptic plasticity, and abolishes neurodegeneration-associated memory impairments. These findings advocate for the development of selective inhibitors of histone deacetylase 2 and suggest that cognitive capacities following neurodegeneration are not entirely lost, but merely impaired by this epigenetic blockade.en_US
dc.language.isoen_USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofdoi:10.1038/nature10849en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3498952/pdf/en_US
dash.licenseLAA
dc.subjectneuroscienceen_US
dc.subjectdiseaseen_US
dc.subjectmolecular biologyen_US
dc.subjectanimal behavioren_US
dc.titleAn Epigenetic Blockade of Cognitive Functions in the Neurodegenerating Brainen_US
dc.typeJournal Articleen_US
dc.description.versionAccepted Manuscripten_US
dc.relation.journalNatureen_US
dash.depositing.authorHaggarty, Stephen John
dc.date.available2013-04-23T13:14:42Z
dc.identifier.doi10.1038/nature10849*
dash.authorsorderedfalse
dash.contributor.affiliatedNieland, Thomas
dash.contributor.affiliatedHaggarty, Stephen


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