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.
Keywords:
DNA methylation; brain and neurodegeneration; epigenetics; hippocampus.
Copyright © 2014 The Authors. Hippocampus Published by Wiley Periodicals, Inc.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Aged, 80 and over
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Alzheimer Disease / genetics
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Alzheimer Disease / metabolism*
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Cell Line, Tumor
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Cyclic AMP Response Element-Binding Protein / metabolism*
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Cyclic AMP-Dependent Protein Kinases / metabolism*
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Dual-Specificity Phosphatases / genetics
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Dual-Specificity Phosphatases / metabolism*
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Epigenesis, Genetic
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Female
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Gene Expression
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Hippocampus / metabolism*
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Humans
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Male
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Methylation
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Mitogen-Activated Protein Kinase Phosphatases / genetics
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Mitogen-Activated Protein Kinase Phosphatases / metabolism*
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Phosphorylation
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Promoter Regions, Genetic / physiology
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Signal Transduction / physiology
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tau Proteins / metabolism*
Substances
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CREB1 protein, human
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Cyclic AMP Response Element-Binding Protein
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MAPT protein, human
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tau Proteins
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Cyclic AMP-Dependent Protein Kinases
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Mitogen-Activated Protein Kinase Phosphatases
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DUSP22 protein, human
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Dual-Specificity Phosphatases