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组蛋白去乙酰化酶抑制剂:神经紊乱治疗的关键?

Histone Deacetylase Inhibitors: A Therapeutic Key in Neurological Disorders?

机构信息

NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.

出版信息

J Neuropathol Exp Neurol. 2018 Oct 1;77(10):855-870. doi: 10.1093/jnen/nly073.

Abstract

Understanding the contribution of imbalance in protein acetylation levels and dysfunction of transcription to neurodegenerative diseases provides the rationale for the use of epigenetic modulators such as histone deacetylase (HDAC) inhibitors to combat neurodegenerative conditions. It is now widely recognized that various low-molecular weight HDAC inhibitors are broadly neuroprotective, preventing or delaying neuronal death and dysfunction in many rodent models of neurodegeneration. The beneficial effects result in part from modifications of histones and nonhistone proteins. This review describes evidence indicating that HDAC inhibitors have emerged as a promising new strategy in treating neurodegenerative disorders and summarizes treatment strategies from clinical trials currently underway.

摘要

了解蛋白质乙酰化水平失衡和转录功能障碍对神经退行性疾病的贡献,为使用表观遗传调节剂(如组蛋白去乙酰化酶(HDAC)抑制剂)来对抗神经退行性疾病提供了依据。现在人们普遍认识到,各种低分子量 HDAC 抑制剂具有广泛的神经保护作用,可预防或延迟许多神经退行性疾病啮齿动物模型中的神经元死亡和功能障碍。这些有益的效果部分归因于组蛋白和非组蛋白的修饰。本文综述了表明 HDAC 抑制剂已成为治疗神经退行性疾病的一种有前途的新策略的证据,并总结了目前正在进行的临床试验中的治疗策略。

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