m6A修饰在神经系统疾病中的作用

Roles of m6A modification in neurological diseases

N6-甲基腺苷(N6-methyladenosine,m6A)甲基化修饰是真核生物mRNA最常见的表观遗传修饰之一,在相关酶的催化调控下,m6A通过介导RNA转录、剪接、翻译、衰变等参与机体的生理和病理生理过程。以往主要关注m6A在肿瘤,如血液系统肿瘤、宫颈癌、乳腺癌等中的调控作用,近年来发现m6A富集于与神经发生、细胞周期、神经元分化等相关的mRNA中,其在神经系统中的调控作用逐渐被重视。m6A修饰水平及相关酶蛋白表达水平发生改变会引起神经系统功能紊乱,参与神经系统疾病的发生与转归。m6A修饰及其相关酶在重度抑郁症、帕金森病、阿尔茨海默症、脆性X综合征、肌萎缩侧索硬化、创伤性脑损伤及神经系统肿瘤等众多神经系统疾病的发展进程中扮演关键角色。

N6-methyladenosine(m6A)methylation modification is one of the most common epigenetic modifications for eukaryotic m RNA.Under the catalytic regulation of relevant enzymes,m6A participates in the body’s pathophysiological processes via mediating RNA transcription,splicing,translation,and decay.In the past,we mainly focused on the regulation of m6A in tumors such as hematological tumors,cervical cancer,breast cancer.In recent years,it has been found that m6A is enriched in m RNAs of neurogenesis,cell cycle,and neuron differentiation.Its regulation in the nervous system is gradually being recognized.When the level of m6A modification and the expression levels of relevant enzyme proteins are changed,it will cause neurological dysfunction and participate in the occurrence and conversion of neurological diseases.Recent studies have found that the m6A modification and its associated enzymes were involved in major depressive disorder,Parkinson’s disease,Alzheimer’s disease,Fragile X syndrome,amyotrophic lateral sclerosis,and traumatic brain injury,and they also play a key role in the development of neurological diseases and many other neurological diseases.This paper mainly reviewed the recent progress of m6A modification-related enzymes,focusing on the impact of m6A modification and related enzyme-mediated regulation of gene expression on the central nervous system diseases,so as to provide potential targets for the prevention of neurological diseases.