《生命科学》 2021, 33(5): 621-629

内质网-线粒体结构偶联在内质网应激中的作用及其与阿尔茨海默病的关联性

周鹤妍 , 孙谕莹 , 黄汉昌^*

北京联合大学生物活性物质与功能食品北京市重点实验室，北京 100191

摘　要：

阿尔茨海默病(Alzheimer’s disease, AD) 是老年人中最常见的神经退行性疾病之一，以在大脑中细胞外β- 淀粉样蛋白沉积形成老年斑和神经元内tau 蛋白过度磷酸化形成神经纤维原缠结为主要病理特征。AD 的病因目前以tau 蛋白磷酸化、Aβ 蛋白的沉积和代谢紊乱假说为主，但确切的机制尚未明确。内质网-线粒体结构偶联又称线粒体相关内质网膜(mitochondria-associated ER membranes, MAM)，近年来MAM 在内质网应激中的作用得到广泛的关注。许多研究表明MAM 与AD 的发生有密切的联系。Ca2+ 稳态是维持细胞正常生命活动所必需的，当MAM 完整性遭到破坏，会直接或间接地导致Ca2+ 稳态失衡和氧化应激，Ca2+ 浓度异常则会触发内质网应激，从 而导致神经元死亡，引发AD。该文介绍了MAM 对内质网应激的调节作用，评述了MAM 与AD 发生的关联性。

通讯作者：黄汉昌 , Email:hanchang@buu.edu.cn

Role of mitochondria-associated ER membranes in endoplasmic reticulum stress and its association with Alzheimer's disease

ZHOU He-Yan , SUN Yu-Ying , HUANG Han-Chang^*

Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, Beijing 100191, China

Abstract:

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases in the elderly. The main pathological features in the brain are the formations of senile plaques outside the cells containing amyloid-β (Aβ) and neurofibrillary tangles composed of hyperphosphorylated tau protein in neurons. At present, the etiology of AD is mainly based on the hypothesis of Aβ deposition, tau protein phosphorylation, and metabolic disorders, but the exact mechanism is not yet clear. The coupling structure between mitochondria and endoplasmic reticulum (ER) is also known as mitochondria-associated ER membranes (MAM). In recent years, the role of MAM in endoplasmic reticulum stress has been paid widespread attention to. Many studies have shown that MAM is closely related to the occurrence of AD. Ca2+ homeostasis is necessary to maintain the physiological activities of cells. When the integrity of MAM is damaged, it will directly or indirectly lead to the imbalance of Ca2+ homeostasis and oxidative stress. Abnormal Ca2+ will trigger ER stress, lead to neuronal death and cause AD. This article introduces the regulation and role of MAM on the endoplasmic reticulum stress and reviews the potential association of MAM with the AD development.

Communication Author：HUANG Han-Chang , Email:hanchang@buu.edu.cn