组蛋白去乙酰化酶在神经退行性疾病发病机制中的研究进展  

Histone deacetylases in pathogenesis of neurodegenerative diseases

作　　者：孟玉洁 周世越 宋丹丹 张庆硕 韩晓旭 许顺良[1] MENG Yujie;ZHOU Shiyue;SONG Dandan;ZHAGN Qingshuo;HAN Xiaoxu;XU Shunliang(The Second Hospital,Shandong University,Ji’nan 250033,China)

机构地区：[1]山东大学第二医院,山东济南250033

出　　处：《中国实用神经疾病杂志》2022年第4期498-502,共5页Chinese Journal of Practical Nervous Diseases

基　　金：山东省自然科学基金(编号:2019GSF108066,ZR2015HM024)。

摘　　要：组蛋白乙酰化是表观遗传调控的主要机制之一,由组蛋白乙酰转移酶(histone acetyltransferases,HATs)和组蛋白去乙酰化酶(histone deacetylases,HDACs)共同调控。近年研究发现,HDACs通过调节错误折叠蛋白的异常积聚、线粒体功能、氧化应激等,与帕金森病(Parkinson’s disease,PD)、阿尔茨海默病(Alzheimer’s disease,AD)、亨廷顿病(Huntington’s disease,HD)等多种神经退行性疾病(neurodegenerative diseases,NDs)的发病机制密切相关。在NDs中,组蛋白乙酰化稳态被破坏,向低乙酰化方向转移。越来越多的研究提出了组蛋白去乙酰化酶抑制剂(histone deacetylase inhibitor,HDACi)可用于治疗某些神经退行性疾病的可能性。本文对HADCs在NDs发病机制中的研究进展进行综述。Histone acetylation is one of the main mechanisms of epigenetic regulation,co-regulated by his⁃tone acetyltransferases(HATs)and histone deacetylases(HDACs).HDACs can deacetylate lysine residues of his⁃tones and non-histone proteins,regulating almost all biological processes in cells.Many experimental models have confirmed that HDACs are closely related with the pathogenesis of neurodegenerative diseases(NDs)through regu⁃lation for deposition of aggregate-prone proteins,mitochondrial function,oxidative stress,etc.In NDs,histone acety⁃lation homeostasis is disrupted,shifting towards hypoacetylation.Recently,a growing number of studies have raised the possibility that histone deacetylase inhibitor(HDACi)could be used to treat some DAs.In this review,we discuss the latest research progress on the comprehensive role of HDACs in pathogenesis of NDs and the possi⁃ble therapeutic target for treating some NDs.

关 键 词：组蛋白去乙酰化酶 HDACS 神经退行性疾病 帕金森病 阿尔茨海默病 

分 类 号：R741[医药卫生—神经病学与精神病学]