表观遗传修饰在神经退行性变性疾病中的作用研究进展  

The roles of epigenetic modifications in neurodegenerative diseases

作　　者：曲文政 庄英粮 李学坤 QU Wenzheng;ZHUANG Yingliang;LI Xuekun(Children's Hospital,Zhejiang University School of Medicine,National Clinical Research Center for Child Health,National Children's Regional Medical Center,Hangzhou 310052,China;Institute of Translational Medicine,Zhejiang University,Hangzhou 310029,China)

机构地区：[1]浙江大学医学院附属儿童医院,国家儿童健康与疾病临床医学研究中心,国家儿童区域医疗中心,浙江杭州310052 [2]浙江大学转化医学研究院,浙江杭州310029

出　　处：《浙江大学学报（医学版）》2021年第5期642-650,共9页Journal of Zhejiang University(Medical Sciences)

基　　金：国际科技合作重点项目计划(YS2017YFGH001214);国家自然科学基金(92049108)。

摘　　要：表观遗传修饰对神经发育、神经干细胞命运决定和神经系统的生理功能发挥具有重要的调节作用。异常的表观遗传修饰与阿尔茨海默病、帕金森病和亨廷顿病等神经退行性变性疾病的发生和发展有密切关系:异常升高的DNA甲基化修饰抑制了一些修复基因的表达,影响亨廷顿病进展;阿尔茨海默病患者大脑中H3K27ac和H3K9ac组蛋白修饰增加,影响神经变性;RNA甲基化修饰在阿尔茨海默病和帕金森病两种疾病动物模型中呈现差异化的改变。因此,表观遗传修饰可能作为神经系统疾病的潜在治疗靶点。本文综述了表观遗传修饰参与神经退行性变性疾病及其分子机制的最新研究进展。In neuronal system,epigenetic modifications are essential for neuronal development,the fate determination of neural stem cells and neuronal function.The dysfunction of epigenetic regulation is closely related to occurrence and development of neurodegenerative diseases,including Alzheimer’s disease,Parkinson’s disease,Huntington’s disease.Abnormally elevated DNA methylation inhibits the expression of some DNA repair-related genes and affects the progression of Huntington’s disease.In the brain of Alzheimer’s disease patients,the levels of H3K27ac and H3K9ac histone modifications increased.In addition,the alteration of RNA methylation in animal models of Alzheimer’s disease and Parkinson’s disease showed discrepancy trends.Therefore,epigenetic modifications may serve as potential therapeutic targets for neurodegenerative diseases.Here,we summarize the recent progress of the roles of epigenetic modifications in neurodegenerative diseases.

关 键 词：表观遗传学 DNA修饰 组蛋白修饰 RNA修饰 阿尔茨海默病 帕金森病 亨廷顿病 综述 

分 类 号：R394[医药卫生—医学遗传学] R741[医药卫生—基础医学]