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组蛋白去乙酰化酶作为治疗人类神经退行性疾病的靶点。

Histone deacetylases as targets for the treatment of human neurodegenerative diseases.

作者信息

D'Mello Santosh R

机构信息

Department of Molecular and Cell Biology, University of Texas, Dallas, Texas, USA.

出版信息

Drug News Perspect. 2009 Nov;22(9):513-24. doi: 10.1358/dnp.2009.9.1428871.

Abstract

Histone deacetylases (HDACs) are a family of proteins that play an important role in regulating transcription as well as the function of a variety of cellular proteins. While these proteins are expressed abundantly in the brain, little is known about their roles in brain function. A growing body of evidence suggests that HDACs regulate neuronal survival. Results from studies conducted in vertebrate and mammalian experimental systems indicate that while some of these proteins are involved in promoting neuronal death, a majority of the HDACs studied thus far protect against neurodegeneration. Here we review the research performed on the role played by individual members of the HDAC family in the regulation of neuronal death. Chemical inhibitors of HDACs have been used in a variety of models of neurodegenerative disorders. We summarize the results from these studies, which indicate that HDAC inhibitors show great promise as therapeutic agents for human neurodegenerative disorders.

摘要

组蛋白去乙酰化酶(HDACs)是一类蛋白质家族,在调节转录以及多种细胞蛋白的功能方面发挥着重要作用。虽然这些蛋白质在大脑中大量表达,但人们对它们在脑功能中的作用知之甚少。越来越多的证据表明,HDACs调节神经元存活。在脊椎动物和哺乳动物实验系统中进行的研究结果表明,虽然其中一些蛋白质参与促进神经元死亡,但迄今为止研究的大多数HDACs可预防神经退行性变。在此,我们综述了关于HDAC家族个别成员在调节神经元死亡中所起作用的研究。HDACs的化学抑制剂已被用于多种神经退行性疾病模型。我们总结了这些研究的结果,这些结果表明HDAC抑制剂作为人类神经退行性疾病的治疗药物具有巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4231/3934413/7fa3a8773952/nihms555774f1.jpg

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