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: Sanchez-Mut, Jose Vicente, Aso Pérez, Ester, Heyn, Holger, Matsuda, Tadashi, Bock, Christoph, Ferrer, Isidro (Ferrer Abizanda), Esteller, Manel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/111024
Acceso en línea:https://hdl.handle.net/2445/111024
Access Level:acceso abierto
Palabra clave:Epigènesi
Metilació
ADN
Hipocamp (Cervell)
Malaltia d'Alzheimer
Malalties neurodegeneratives
Epigenesis
Methylation
DNA
Hippocampus (Brain)
Alzheimer's disease
Neurodegenerative Diseases
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.