TREM2在神经退行性疾病中的作用机制及治疗潜力

TREM2 in Neurodegenerative Diseases: Mechanisms and Therapeutic Potential.

作者信息

Li Ling, Zheng Xiaoxiao, Ma Hongyue, Zhu Mingxia, Li Xiuli, Sun Xiaodan, Feng Xinhong

机构信息

Department of Neurology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing 102218, China.

Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China.

出版信息

Cells. 2025 Sep 5;14(17):1387. doi: 10.3390/cells14171387.

DOI:10.3390/cells14171387

PMID:40940798

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12428023/

Abstract

Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), represent significant global health challenges, affecting millions and straining healthcare systems. These disorders involve progressive neuronal loss and cognitive decline, with incompletely elucidated underlying mechanisms. Chronic neuroinflammation is increasingly recognized as a critical contributor to disease progression. The brain's resident immune cells, microglia, are central to this inflammatory response. When overactivated, microglia and other immune cells, such as peripheral macrophages, can exacerbate inflammation and accelerate disease development. Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) is a transmembrane receptor of the immunoglobulin superfamily that demonstrates high expression on microglia in the central nervous system. TREM2 serves a vital role in regulating phagocytosis, synaptic pruning, and energy metabolism. This review examines the functions of TREM2 in neurodegenerative diseases and its potential as a therapeutic target, aiming to inform future treatment strategies.

摘要

神经退行性疾病，包括阿尔茨海默病（AD）、帕金森病（PD）和肌萎缩侧索硬化症（ALS），是全球重大的健康挑战，影响着数百万人并给医疗系统带来压力。这些疾病涉及神经元的进行性丧失和认知衰退，其潜在机制尚未完全阐明。慢性神经炎症越来越被认为是疾病进展的关键因素。大脑中的常驻免疫细胞——小胶质细胞，是这种炎症反应的核心。当过度激活时，小胶质细胞和其他免疫细胞，如外周巨噬细胞，会加剧炎症并加速疾病发展。髓系细胞表达的触发受体2（TREM2）是免疫球蛋白超家族的跨膜受体，在中枢神经系统的小胶质细胞上高表达。TREM2在调节吞噬作用、突触修剪和能量代谢中起着至关重要的作用。本综述探讨了TREM2在神经退行性疾病中的功能及其作为治疗靶点的潜力，旨在为未来的治疗策略提供参考。