Promoter hypermethylation of the phosphatase DUSP22 mediates PKA-dependent TAU phosphorylation and CREB activation in Alzheimer's disease

ABSTRACT 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. Usi...

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Bibliographic Details
Published in:Hippocampus 2014-04, Vol.24 (4), p.363-368
Main Authors: Sanchez-Mut, Jose Vicente, Aso, Ester, Heyn, Holger, Matsuda, Tadashi, Bock, Christoph, Ferrer, Isidre, Esteller, Manel
Format: Article
Language:English
Subjects:
ADN
Aged
Aged, 80 and over
Alzheimer Disease - genetics
Alzheimer Disease - metabolism
Alzheimer's disease
brain and neurodegeneration
Cell Line, Tumor
Cyclic AMP Response Element-Binding Protein - metabolism
Cyclic AMP-Dependent Protein Kinases - metabolism
DNA
DNA methylation
Dual-Specificity Phosphatases - genetics
Dual-Specificity Phosphatases - metabolism
Epigenesis
Epigenesis, Genetic
epigenetics
Epigènesi
Female
Gene Expression
Hipocamp (Cervell)
hippocampus
Hippocampus (Brain)
Hippocampus - metabolism
Humans
Malaltia d'Alzheimer
Malalties neurodegeneratives
Male
Methylation
Metilació
Mitogen-Activated Protein Kinase Phosphatases - genetics
Mitogen-Activated Protein Kinase Phosphatases - metabolism
Neurodegenerative diseases
Phosphorylation
Promoter Regions, Genetic - physiology
Rapid Communication
Signal Transduction - physiology
tau Proteins - metabolism
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Summary:ABSTRACT 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.
ISSN:1050-9631
1098-1063
DOI:10.1002/hipo.22245