m^(6)A修饰与阿尔茨海默病的研究进展

Research advances in m^(6)A modification and Alzheimer disease

N^(6)-腺苷甲基化(N^(6)-adenosine methylation,m^(6)A)是将S-腺苷甲硫氨酸提供的甲基添加到腺苷N^(6)位点的表观遗传修饰,在20世纪70年代被鉴定出来,占成人大脑中全部信使RNA(messenger mRNA)碱基甲基化的80%以上^([1]),还可发生在微小RNA、长链非编码RNA(long noncoding RNA,lncRNA)、环状RNA(circular RNA,circRNA)、转运RNA(transfer RNA,tRNA)和核糖体RNA中^([2])。

As a common and heterogeneous type of neurodegenerative dementia with a long course and com‐plex pathogenesis,Alzheimer disease(AD)mostly occurrs in middle-aged and elderly people.N^(6)-adenosine methylation(m^(6)A)is the most abundant mRNA modification in eukaryotes with dynamic and reversible features.A large number of studies have shown that enzymes involved in m^(6)A modification could recognize RRACH sequences in target RNA and medi‐ate post-transcriptional translation or degradation of target RNA,as a key molecular factor in the pathogenesis of AD.This paper reviewed the involvement of m^(6)A modification in amyloid plaque,tau protein hyperphosphorylation,microglial acti‐vation-mediated neuroinflammation,and glial and synaptic plasticity,so as to reveal the existing early evidence of m^(6)A's involvement in the pathological mechanism,thus providing theoretical support for seeking early biomarkers and experimen‐tal evidence for AD in the future.