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神经退行性疾病中的表观遗传学:组蛋白去乙酰化酶的作用。

Epigenetics in Neurodegenerative Diseases: The Role of Histone Deacetylases.

机构信息

Department of Pharmacy, Birla Institute of Technology and Science, Pilani-333031, Rajasthan, India.

出版信息

CNS Neurol Disord Drug Targets. 2019;18(1):11-18. doi: 10.2174/1871527317666181004155136.

Abstract

BACKGROUND & OBJECTIVE: Imbalance in histone acetylation levels and consequently the dysfunction in transcription are associated with a wide variety of neurodegenerative diseases. Histone proteins acetylation and deacetylation is carried out by two opposite acting enzymes, histone acetyltransferases and histone deacetylases (HDACs), respectively. In-vitro and in-vivo animal models of neurodegenerative diseases and post mortem brains of patients have been reported overexpressed level of HDACs. In recent past numerous studies have indicated that HDAC inhibitors (HDACIs) might be a promising class of therapeutic agents for treating these devastating diseases. HDACs being a part of repressive complexes, the outcome of their inhibition has been attributed to enhanced gene expression due to heightened histone acetylation. Beneficial effects of HDACIs has been explored both in preclinical and clinical studies of these diseases. Thus, their screening as future therapeutics for neurodegenerative diseases has been widely explored.

CONCLUSION

In this review, we focus on the putative role of HDACs in neurodegeneration and further discuss their potential as a new therapeutic avenue for treating neurodegenerative diseases.

摘要

背景与目的

组蛋白乙酰化水平失衡以及随之而来的转录功能障碍与多种神经退行性疾病有关。组蛋白的乙酰化和去乙酰化分别由两种相反作用的酶——组蛋白乙酰转移酶和组蛋白去乙酰化酶(HDACs)来完成。在神经退行性疾病的体外和体内动物模型以及患者的尸检大脑中,已有报道称 HDACs 表达水平升高。最近的许多研究表明,HDAC 抑制剂(HDACIs)可能是治疗这些毁灭性疾病的一类有前途的治疗药物。HDACs 作为抑制复合物的一部分,其抑制作用的结果归因于由于组蛋白乙酰化增加而导致的基因表达增强。在这些疾病的临床前和临床研究中都探索了 HDACIs 的有益作用。因此,它们作为神经退行性疾病未来治疗药物的筛选已得到广泛探索。

结论

在这篇综述中,我们重点讨论了 HDACs 在神经退行性变中的假定作用,并进一步讨论了它们作为治疗神经退行性疾病的新治疗途径的潜力。

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