Therapeutic application of histone deacetylase inhibitors for central nervous system disorders

被引：598

作者：

Kazantsev, Aleksey G. ^{[1
]}

Thompson, Leslie M. ^{[2
,3
,4
]}

机构：

[1] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Neurodegenerat Dis, Charlestown, MA 02129 USA

[2] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92697 USA

[3] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA 92697 USA

[4] Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92697 USA

来源：

NATURE REVIEWS DRUG DISCOVERY | 2008年 / 7卷 / 10期

关键词：

D O I：

10.1038/nrd2681

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Histone deacetylases (HDACs) - enzymes that affect the acetylation status of histones and other important cellular proteins - have been recognized as potentially useful therapeutic targets for a broad range of human disorders. Pharmacological manipulations using small-molecule HDAC inhibitors - which may restore transcriptional balance to neurons, modulate cytoskeletal function, affect immune responses and enhance protein degradation pathways - have been beneficial in various experimental models of brain diseases. Although mounting data predict a therapeutic benefit for HDAC-based therapy, drug discovery and development of clinical candidates face significant challenges. Here, we summarize the current state of development of HDAC therapeutics and their application for the treatment of human brain disorders such as Rubinstein - Taybi syndrome, Rett syndrome, Friedreich's ataxia, Huntington's disease and multiple sclerosis.

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页码：854 / 868

页数：15

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