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dc.creatorRicobaraza, A. (Ana)-
dc.creatorCuadrado-Tejedor, M. (Mar)-
dc.creatorPerez-Mediavilla, L.A. (Luis Alberto)-
dc.creatorFrechilla, D. (Diana)-
dc.creatorRio, J. (Joaquín) del-
dc.creatorGarcia-Osta, A. (Ana)-
dc.date.accessioned2011-02-10T15:36:02Z-
dc.date.available2011-02-10T15:36:02Z-
dc.date.issued2009-06-
dc.identifier.citationRicobaraza A, Cuadrado-Tejedor M, Perez-Mediavilla A, Frechilla D, Del Rio J, Garcia-Osta A. Phenylbutyrate ameliorates cognitive deficit and reduces tau pathology in an Alzheimer's disease mouse model. Neuropsychopharmacology 2009 Jun;34(7):1721-1732.es_ES
dc.identifier.issn0893-133X-
dc.identifier.urihttps://hdl.handle.net/10171/16437-
dc.description.abstractChromatin modification through histone acetylation is a molecular pathway involved in the regulation of transcription underlying memory storage. Sodium 4-phenylbutyrate (4-PBA) is a well-known histone deacetylase inhibitor, which increases gene transcription of a number of genes, and also exerts neuroprotective effects. In this study, we report that administration of 4-PBA reversed spatial learning and memory deficits in an established mouse model of Alzheimer’s disease (AD) without altering b-amyloid burden. We also observed that the phosphorylated form of tau was decreased in the AD mouse brain after 4-PBA treatment, an effect probably due to an increase in the inactive form of the glycogen synthase kinase 3b (GSK3b). Interestingly, we found a dramatic decrease in brain histone acetylation in the transgenic mice that may reflect an indirect transcriptional repression underlying memory impairment. The administration of 4-PBA restored brain histone acetylation levels and, as a most likely consequence, activated the transcription of synaptic plasticity markers such as the GluR1 subunit of the AMPA receptor, PSD95, and microtubule-associated protein-2. The results suggest that 4-PBA, a drug already approved for clinical use, may provide a novel approach for the treatment of AD.es_ES
dc.language.isoenges_ES
dc.publisherNature Publishing Groupes_ES
dc.rightsinfo:eu-repo/semantics/closedAccess-
dc.subjectAlzheimer’s diseasees_ES
dc.subjectPhenylbutyratees_ES
dc.subjectHistone deacetylasees_ES
dc.subjectGSK3bes_ES
dc.subjectMemoryes_ES
dc.titlePhenylbutyrate ameliorates cognitive deficit and reduces tau pathology in an Alzheimer's disease mouse modeles_ES
dc.typeArticuloes_ES
dc.identifier.doihttp://dx.doi.org/10.1038/npp.2008.229es_ES

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