Roles of TREM2 in the Pathological Mechanism and the Therapeutic Strategies of Alzheimer’s Disease

IF 4.3 Q2 BUSINESS
M. Lin, J.-X. Yu, W.-X. Zhang, F.-X. Lao, Han-Chang Huang
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Abstract

Alzheimer’s disease (AD) is an age-related degenerative disease, which is characteristic by the deposition of senile plaques (SP) outside the cells, the neurofibrillary tangles (NFTs) inside the neurons, and the loss of synapse and neurons. Neuroinflammation may play an important role in the pathogenesis of AD. Microglia are the immune cells in the central nervous system. However, microglia might become disease-related microglia (DAMs) when stimulated by the external environment. DAMs have been shown to be involved in a series of events of AD development including Aβ accumulation and tau phosphorylation. The triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane receptor that is mainly expressed by microglia in the central nervous system (CNS). TREM2 plays an important role in the physiological function of microglia, and the dyshomeostasis of TREM2 is related to the development of late-onset AD. This article summarized the latest advances in TREM2 biology and its impact on the roles of microglia in AD development, with a particular emphasis on the structure, ligands, signal transduction, and the agonistic antibodies of TREM2 for AD treatment. We further discussed the survival, migration, phagocytosis, inflammation, and cellular metabolism of microglia, as well as the role of sTREM2 in neuroprotection and as a biomarker for AD. It provides a reference for further research on the molecular mechanism of microglial TREM2 in the occurrence and development of AD and on the therapeutic strategies targeted on the microglial TREM2.

Abstract Image

TREM2 在阿尔茨海默病的病理机制和治疗策略中的作用
阿尔茨海默病(AD)是一种与年龄有关的退行性疾病,其特征是细胞外沉积老年斑(SP)、神经元内沉积神经纤维缠结(NFT)以及突触和神经元的丧失。神经炎症可能在老年痴呆症的发病机制中扮演重要角色。小胶质细胞是中枢神经系统中的免疫细胞。然而,当受到外部环境刺激时,小胶质细胞可能会变成与疾病相关的小胶质细胞(DAMs)。已有研究表明,小胶质细胞参与了AD发展过程中的一系列事件,包括Aβ积累和tau磷酸化。髓系细胞上表达的触发受体 2(TREM2)是一种跨膜受体,主要由中枢神经系统(CNS)中的小胶质细胞表达。TREM2在小胶质细胞的生理功能中发挥着重要作用,而TREM2的失衡与晚发性AD的发病有关。本文总结了TREM2生物学的最新进展及其对小胶质细胞在AD发展中的作用的影响,特别强调了TREM2的结构、配体、信号转导和用于AD治疗的激动抗体。我们进一步讨论了小胶质细胞的存活、迁移、吞噬、炎症和细胞代谢,以及 sTREM2 在神经保护和作为 AD 生物标志物中的作用。它为进一步研究小胶质细胞TREM2在AD发生和发展中的分子机制以及针对小胶质细胞TREM2的治疗策略提供了参考。
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来源期刊
The Journal of Prevention of Alzheimer's Disease
The Journal of Prevention of Alzheimer's Disease Medicine-Psychiatry and Mental Health
CiteScore
9.20
自引率
0.00%
发文量
0
期刊介绍: The JPAD Journal of Prevention of Alzheimer’Disease will publish reviews, original research articles and short reports to improve our knowledge in the field of Alzheimer prevention including: neurosciences, biomarkers, imaging, epidemiology, public health, physical cognitive exercise, nutrition, risk and protective factors, drug development, trials design, and heath economic outcomes.JPAD will publish also the meeting abstracts from Clinical Trial on Alzheimer Disease (CTAD) and will be distributed both in paper and online version worldwide.We hope that JPAD with your contribution will play a role in the development of Alzheimer prevention.
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