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Rab蛋白在阿尔茨海默病发病机制中作用的研究进展

张菁¹, 江海天¹, 韩道滨¹, 于卉¹, 王路雯², 苏擘^1,*

¹山东大学基础医学院，济南 250012；²山东大学高等医学研究院，济南 250012

摘要

阿尔茨海默病(Alzheimer’s disease, AD)最显著的两大病理改变为细胞外β淀粉样蛋白(β-amyloid, Aβ)沉积形成的老年斑和神经元内tau蛋白过度磷酸化形成的神经纤维缠结。近来有越来越多的研究显示，多种小GTP酶Ras相关蛋白(Ras-related protein, Rab)与AD发病密切相关。作为细胞内膜类结构转运、加工的关键调节因素，Rab家族蛋白的改变是引发AD中囊泡转运异常的主要因素之一，同时也参与了AD中Aβ、tau等病理改变的发生和发展。本文就Rab蛋白的主要功能及其在AD发病机制中的作用进行了系统综述。

关键词： Rab; 阿尔茨海默病; Aβ; tau; 膜转运

Research advances in the role of Rab GTPases in Alzheimer’s disease

ZHANG Jing¹, JIANG Hai-Tian¹, HAN Dao-Bin¹, YU Hui¹, WANG Lu-Wen², SU Bo^1,*

¹School of Basic Medical Science, Shandong University, Jinan 250012, China；²Advanced Medical Research Institute, Shandong University, Jinan 250012, China

Abstract

Extracellular deposition of β-amyloid (Aβ) and intracellular hyperphosphorylated tau are the predominant pathological changes in Alzheimer’s disease (AD). Increasing evidence demonstrates a critical role of a variety of small GTPases, namely Ras-related proteins (Rabs), in the pathogenesis of AD. As crucial regulators of intracellular membrane trafficking, alteration in Rab protein expression and function represents one of the primary factors contributing to the abnormal membrane trafficking in AD. Additionally, the Rab GTPases are also involved in the development of Aβ, tau and other pathological changes associated with AD. In this article, we conduct a comprehensive review on the primary functions of multiple Rab proteins and their involvement in the pathogenesis of AD. 

Key words: Rab; Alzheimer’s disease; Aβ; tau; membrane trafficking

收稿日期：　　录用日期：

通讯作者：苏擘　　E-mail: bxs103@sdu.edu.cn

DOI: 10.13294/j.aps.2023.0076

引用本文：

张菁, 江海天, 韩道滨, 于卉, 王路雯, 苏擘. Rab蛋白在阿尔茨海默病发病机制中作用的研究进展[J]. 生理学报 2023; 75 (6): 817-835.

ZHANG Jing, JIANG Hai-Tian, HAN Dao-Bin, YU Hui, WANG Lu-Wen, SU Bo. Research advances in the role of Rab GTPases in Alzheimer’s disease. Acta Physiol Sin 2023; 75 (6): 817-835 (in Chinese with English abstract).