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

被引：89

作者：

Vicente Sanchez-Mut, Jose ^{[1
]}

Aso, Ester ^{[2
]}

Heyn, Holger ^{[1
]}

Matsuda, Tadashi ^{[3
]}

Bock, Christoph ^{[4
]}

Ferrer, Isidre ^{[2
]}

Esteller, Manel ^{[1
,5
,6
]}

机构：

[1] Bellvitge Biomed Res Inst IDIBELL, Epigenet & Biol Program PEBC, Barcelona, Spain

[2] Univ Barcelona, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Hosp Univ Bellvitge, Neuropathol Inst,Bellvitge Biomed Res Inst IDIBEL, Barcelona, Catalonia, Spain

[3] Hokkaido Univ, Grad Sch Pharmaceut Sci, Dept Immunol, Sapporo, Hokkaido, Japan

[4] Austrian Acad Sci, CeMM Res Ctr Mol Med, A-1010 Vienna, Austria

[5] Univ Barcelona, Sch Med, Dept Physiol Sci 2, Barcelona, Catalonia, Spain

[6] Inst Catalana Recerca & Estudis Avancats, Barcelona, Catalonia, Spain

来源：

HIPPOCAMPUS | 2014年 / 24卷 / 04期

关键词：

epigenetics; DNA methylation; hippocampus; brain and neurodegeneration; ELEMENT-BINDING PROTEIN; DNA METHYLATION; EPIGENETIC MODIFICATIONS; FRONTAL-CORTEX; MICE LACKING; EXPRESSION; NEURONS; TRANSCRIPTION; DEGENERATION; MECHANISMS;

D O I：

10.1002/hipo.22245

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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. (c) 2014 The Authors. Hippocampus Published by Wiley Periodicals, Inc.

引用

页码：363 / 368

页数：6

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