The BET/BRD inhibitor JQ1 improves brain plasticity in WT and APP mice

被引：59

作者：

Benito, E. ^{[1
]}

Ramachandran, B. ^{[2
]}

Schroeder, H. ^{[1
]}

Schmidt, G. ^{[3
]}

Urbanke, H. ^{[1
]}

Burkhardt, S. ^{[1
]}

Capece, V. ^{[1
]}

Dean, C. ^{[2
]}

Fischer, A. ^{[1
,4
]}

机构：

[1] German Ctr Neurodegenerat Dis DZNE Gottingen, Dept Epigenet & Syst Med Neurodegenerat Dis, Siebold Str 3A, D-37075 Gottingen, Germany

[2] European Neurosci Inst, Trans Synapt Signaling Grp, Gottingen, Germany

[3] Univ Med Ctr Gottingen, Dept Gen Visceral & Pediat Surg, Gottingen, Germany

[4] Univ Med Ctr Gottingen, Dept Psychiat & Psychotherapy, Gottingen, Germany

来源：

TRANSLATIONAL PSYCHIATRY | 2017年 / 7卷

关键词：

EPIGENETIC MECHANISMS; HISTONE ACETYLATION; MEMORY FORMATION; BET; INFLAMMATION; GENE; EXPRESSION; PROTEINS; MODEL; BRD4;

D O I：

10.1038/tp.2017.202

中图分类号：

R749 [精神病学];

学科分类号：

100205 ;

摘要：

Histone acetylation is essential for memory formation and its deregulation contributes to the pathogenesis of Alzheimer's disease. Thus, targeting histone acetylation is discussed as a novel approach to treat dementia. The histone acetylation landscape is shaped by chromatin writer and eraser proteins, while readers link chromatin state to cellular function. Chromatin readers emerged novel drug targets in cancer research but little is known about the manipulation of readers in the adult brain. Here we tested the effect of JQ1-a small- molecule inhibitor of the chromatin readers BRD2, BRD3, BRD4 and BRDT-on brain function and show that JQ1 is able to enhance cognitive performance and long-term potentiation in wild-type animals and in a mouse model for Alzheimer's disease. Systemic administration of JQ1 elicited a hippocampal gene expression program that is associated with ion channel activity, transcription and DNA repair. Our findings suggest that JQ1 could be used as a therapy against dementia and should be further tested in the context of learning and memory.

引用

页码：e1239 / e1239

页数：8

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