基于DNA甲基化探讨非药物疗法防治阿尔茨海默病的可能机制

Possible Mechanism of Non-drug Therapy in Prevention and Treatment of Alzheimer′s Disease Based on DNA Methylation

目前阿尔茨海默病(AD)的病因病机尚未完全明确,DNA甲基化作为表观遗传学组成部分之一,其可能参与了AD的发病过程。目前AD的一线药物仅可缓解症状,疗效和安全性均有待考证,尚无药物能够阻止AD进展。非药物疗法具有多层面、多途径、多靶点的特点,在早期防治AD中发挥关键作用,DNA甲基化调控可能参与了包括中医针灸、经颅电刺激、高压氧疗、运动、饮食等在内的非药物疗法防治AD的过程,其可能的干预机制主要包括调节β淀粉样蛋白的生成、抑制Tau蛋白的磷酸化、维持线粒体的正常功能、影响小胶质细胞的活化、调节关键蛋白表达、促进神经元发生分化与突触发育等。

At present,the etiology and pathogenesis of Alzheimer′s disease(AD)are not fully understood,and DNA methylation,as one of the epigenetic components,may be involved in the pathogenesis of AD.At present,the first-line drugs for AD can only alleviate symptoms,and their efficacy and safety have yet to be proven.There are no drugs that can prevent the progression of AD.Non-drug therapy has the characteristics of multi-level,multi-channel and multi-target,and plays a key role in the early prevention and treatment of AD.DNA methylation regulation may be involved in the process of non-drug therapies to prevent and treat AD,including acupuncture and moxibustion,transcranial electrical stimulation,hyperbaric oxygen therapy,exercise,diet,etc.The possible intervention mechanism mainly includes regulation of the generation ofβamyloid protein,inhibition of Tau protein phosphorylation,maintenance of normal mitochondrial function,influence of microglial cell activation,regulation of key protein expression,promotion of neuronal differentiation and synaptic development,etc.