阿尔茨海默病中线粒体轴突转运障碍的发生机制  

Mechanism of axonal transport dysfuction of mitochondria in Alzheimer's disease

作　　者：沈祎涵 徐涵笑 江林昊 许敏慧 夏天娇[1] Shen Yihan;Xu Hanxiao;Jiang Linhao;Xu Minhui;Xia Tianjiao(Medical School,Nanjing University,Nanjing 210008,China)

机构地区：[1]南京大学医学院,南京210008

出　　处：《中华神经医学杂志》2023年第5期476-479,共4页Chinese Journal of Neuromedicine

摘　　要：阿尔茨海默病(AD)是一种中枢神经退行性疾病,其发病机制目前尚不明确。近年来有研究表明,线粒体轴突转运障碍可能参与AD的进程。正常的线粒体轴突转运过程主要由微管、分子马达和连接蛋白参与,而AD的早期病理改变可以通过干扰这些蛋白来损伤线粒体轴突转运,如积聚的β-淀粉样蛋白(Aβ)会损害分子马达的功能,异常修饰的Tau蛋白会降低微管的稳定性,突变型早老蛋白-1(PS1)可以通过激活糖原合成酶激酶3β(GSK-3β)来诱导部分相关蛋白的磷酸化,使线粒体轴突转运出现障碍,导致突触功能失调。本文围绕AD中线粒体轴突转运障碍可能的发生机制进行综述,以期为AD的治疗提供新思路。Alzheimer's disease(AD)is a central neurodegenerative disease with still unclear pathogenesis.Recent studies have shown that axonal transport dysfuction of mitochondria may contribute to AD progression.Normal mitochondrial axonal transport mainly involves microtubules,molecular motors and connexins,while AD early pathological changes can damage mitochondrial axonal transport by interfering with these proteins:accumulatedβ-amyloid(Aβ)impairs the function of molecular motors;abnormally modified Tau protein reduces microtubule stability;mutant presenilin-1(PS1)can induce phosphorylation of some related proteins by activating glycogen synthase kinase-3β(GSK-3β);all these processes can damage mitochondrial axonal transport,leading to synaptic dysfunction.This review aims to clarify the possible mechanisms of axonal transport dysfuction of mitochondria in AD and provides new ideas for AD treatment.

关 键 词：阿尔茨海默病 线粒体轴突转运 β-淀粉样蛋白 TAU蛋白 早老蛋白-1 

分 类 号：R749.16[医药卫生—神经病学与精神病学]