m^(6)A甲基化对老年神经退行性疾病的调控作用  

The Regulation of m^(6)A Methylation Modification on Aged-Related Neurodegenerative Diseases

作　　者：郑莉芳 史仍飞[2] 饶志坚 ZHENG Li-Fang;SHI Reng-Fei;RAO Zhi-Jian(College of Physical Education,Shanghai University,Shanghai 200444,China;School of Kinesiology,Shanghai University of Sport,Shanghai 200438,China;College of Physical Education,Shanghai Normal University,Shanghai 200234,China)

机构地区：[1]上海大学体育学院运动人体科学教研室,上海200444 [2]上海体育学院运动健康学院运动营养教研室,上海200438 [3]上海师范大学体育学院理论人体教研室,上海200234

出　　处：《中国生物化学与分子生物学报》2023年第12期1712-1719,共8页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金项目(No.32171136);上海大学青年英才启航计划(No.13-G210-22-367)资助。

摘　　要：衰老是机体对环境的生理和心理适应能力下降,最终导致死亡的自然过程,也是各种老年相关疾病发展的驱动因素,特别是神经退行性疾病。常见的老年神经退行性疾病包括阿尔兹海默病(Alzheimer’s disease,AD)、帕金森病(Parkinson’s disease,PD)、肌萎缩侧索硬化症(amyotrophic lateral sclerosis,ALS)等。而以AD和PD为代表的老年神经退行性疾病是21世纪老龄化社会面临的最大健康问题之一。m^(6)A甲基化在多种修饰酶的作用下调控基因转录和翻译,也是最常见的RNA修饰类型。m^(6)A修饰酶表达异常引起m^(6)A甲基化水平失调,从而引起RNA表达紊乱是m^(6)A甲基化参与调控疾病发展的基本机制。近期研究表明,METTL3、FTO在阿尔兹海默病、帕金森病等疾病中发生显著变化,它们通过影响神经炎症、细胞周期、氧化应激等过程参与上述疾病的发生发展。本文以AD和PD为例探讨了m^(6)A修饰对老年神经退行性疾病的调控作用,这将为抗衰老和治疗老年相关疾病提供新的潜在靶点。Aging is a natural process in which organisms’physiological and psychological adaptability to the environment gradually declines,eventually leading to death.Aging is the driving factor for developing various age-related diseases,especially neurodegenerative diseases.Neurodegenerative diseases in the elderly include Alzheimer’s disease(AD),Parkinson’s disease(PD),amyotrophic lateral sclerosis(ALS),and so on.Neurodegenerative diseases in the elderly,represented by AD and PD,are one of the biggest health problems facing the aging society in the 21st century.N6-methyladenosine(m^(6)A)is the most common type of RNA modification,which regulates gene transcription and translation via various modifying enzymes.The abnormal expression of the m^(6)A modifying enzyme causes the disorder of m^(6)A levels and RNA expression,which is the primary mechanism of m^(6)A in regulating disease development.Recent studies have shown that the abnormal expression of m^(6)A modifying enzymes(such as(m^(6)A methyltransferase)METTL3 and(fat mass and obesity-associated protein)FTO)mediate the occurrence and development of Alzheimer’s disease and Parkinson’s disease by regulating oxidative stress,neuroinflammation,cell cycle,and other processes.Here we discuss the regulatory effect of m^(6)A modification on neurodegenerative diseases with AD and PD as examples,which will provide new potential targets for the anti-aging treatments.

关 键 词：m^(6)A甲基化 老年神经退行性疾病 阿尔兹海默病 帕金森病 

分 类 号：Q4[生物学—生理学] Q5