Promoter Hypermethylation of the Phosphatase DUSP22 Mediates PKA-Dependent TAU Phosphorylation and CREB Activation in Alzheimer's Disease

Genetic screening in Alzheimer's disease (AD) has identified only a handful of genes that are mutated in the disorder. Thus, for a very large proportion of patients, the biology of their disease is poorly understood. Epigenetic alterations may provide an explanation in these cases. Using DNA me...

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Detalles Bibliográficos
Autores principales: Sanchez-Mut, Jose Vicente, Aso, Ester, Heyn, Holger, Matsuda, Tadashi, Bock, Christoph, Ferrer, Isidre, Esteller, Manel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2014
Materias:
Rapid Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4233982/
https://www.ncbi.nlm.nih.gov/pubmed/24436131
http://dx.doi.org/10.1002/hipo.22245
Descripción
Sumario:Genetic screening in Alzheimer's disease (AD) has identified only a handful of genes that are mutated in the disorder. Thus, for a very large proportion of patients, the biology of their disease is poorly understood. Epigenetic alterations may provide an explanation in these cases. Using DNA methylation profiles of human hippocampus from controls and patients, we have identified the presence of promoter hypermethylation of the dual-specificity phosphatase 22 (DUSP22) gene in AD. DUSP22 is a likely candidate gene for involvement in the pathogenesis of the disorder since, as we demonstrate here, it inhibits PKA activity and thereby determines TAU phosphorylation status and CREB signaling. © 2014 The Authors. Hippocampus Published by Wiley Periodicals, Inc.

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