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Dadun > Depósito Académico > Facultad de Ciencias > Departamento de Histología y Anatomía Patológica > DA - Ciencias - HAP - Artículos de revista >

Phenylbutyrate ameliorates cognitive deficit and reduces tau pathology in an Alzheimer's disease mouse model
Authors: Ricobaraza, A. (Ana)
Cuadrado-Tejedor, M. (Mar)
Perez-Mediavilla, L.A. (Luis Alberto)
Frechilla, D. (Diana)
Rio, J. (Joaquín) del
Garcia-Osta, A. (Ana)
Keywords: Alzheimer’s disease
Phenylbutyrate
Histone deacetylase
GSK3b
Memory
Issue Date: Jun-2009
Publisher: Nature Publishing Group
Publisher version: http://dx.doi.org/10.1038/npp.2008.229
ISSN: 0893-133X
Citation: Ricobaraza 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.
Abstract
Chromatin 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.
Permanent link: http://hdl.handle.net/10171/16437
Appears in Collections:DA - CIMA - Neurociencias - Neurofarmacología y conducta - Artículos de Revista
DA - Ciencias - HAP - Artículos de revista
DA - Ciencias - Bioquímica y Biología molecular - Artículos de Revista

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