《生命科学》 2023, 35(11): 1484-1497

小胶质细胞TREM2调控阿尔茨海默病发生的机制研究进展

姜敏艳¹ , 汪　旭^1,2 , 郭锡汉^1,*

¹云南师范大学生命科学学院，生物能源持续开发与利用教育部工程研究中心， 昆明 650500 ²台州耶大基因与细胞治疗研究院，台州 318000

摘　要：

阿尔茨海默病(AD) 是最常见的一种神经退行性疾病，具有多因异质性的特点，具体致病原因尚不清晰。小胶质细胞是常驻于中枢神经系统中的巨噬细胞，负责细胞吞噬、突触修剪、能量代谢等。髓系细胞触发受体2 (TREM2) 是一种主要存在于小胶质细胞表面的受体，对小胶质细胞的功能稳态至关重要。TREM2 R47H 和R62H 两个变异体会增加个体晚发性AD 风险，该发现使TREM2 成为AD 领域一个新的研究热点。本文主要围绕小胶质细胞TREM2 的结构、表达调控、信号转导、功能及其在AD 中的病理学作用等多个方面进行系统性综述，以期在加深理解TREM2 的同时，为深入研究小胶质细胞TREM2 表达和功能异常在AD 发生发展中的作用和分子机制提供参考。

通讯作者：郭锡汉 , Email:guo_xihan@163.com

Advances in the mechanistic study of Alzheimer's disease pathogenesis regulated by microglia TREM2

JIANG Min-Yan¹ , WANG Xu^1,2 , GUO Xi-Han^1,*

¹Engineering Research Center for Sustainable Development and Utilization of Bioenergy, Ministry of Education, College of Life Sciences, Yunnan Normal University, Kunming 650500, China ²Taizhou Yeda Research Institute of Gene and Cell Therapy, Taizhou 318000, China

Abstract:

Alzheimer’s disease (AD) is the most common neurodegenerative disease and is thought to be the result of the interaction of genetic and  environmental factors. The cause of AD is still unclear. TREM2 (trigger receptor 2 expressed on myeloid cells) is a type of  cell surface receptor mainly located on the membrane surface of microglia, and exerts critical role to maintain the  functional homeostasis of microglia. Since two variants of TREM2, R47H and R62H, were linked to the increased risk of AD, microglia have been a new research hot point in AD. In this review, we summarize the structure, expression regulation, signal transduction, function of microglia TREM2 and its pathological role in AD. This review will deepen our understanding of TREM2 and provide novel insights into future studies on the role of microglia TREM2 variation in AD onset and development and the  underlying molecular mechanism.

Communication Author：GUO Xi-Han , Email:guo_xihan@163.com