Microglial TREM2 in amyotrophic lateral sclerosis.

Microglial TREM2 in amyotrophic lateral sclerosis.
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DOI:
10.1002/dneu.22864
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发表时间:
2022-01
影响因子:
3
通讯作者:
Wu LJ
Wu LJ
中科院分区:
医学3区
文献类型:
--
作者:
Xie M;Zhao S;Bosco DB;Nguyen A;Wu LJ

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肌萎缩侧索硬化症(ALS),也称为Lou Gehrig病,是一种侵袭性运动神经元退行性疾病,其特征在于上和下运动神经元的选择性丧失。疾病发生和进展的机制知之甚少。非运动神经轴的参与强调了神经胶质细胞在疾病进展中的作用。小胶质细胞是神经胶质细胞的一个独特亚群,是中枢神经系统(CNS)中的主要免疫细胞。髓样细胞表达触发受体2(TREM2)是一种表面受体,在中枢神经系统内,仅在小胶质细胞上表达,并在小胶质细胞增殖、迁移、活化、代谢和吞噬作用中起关键作用。遗传证据已将TREM2与包括ALS在内的神经退行性疾病联系起来,但其在ALS发病机制中的功能在很大程度上尚不清楚。在这篇综述中,我们总结了小胶质细胞激活(特别关注TREM 2功能)如何在临床和实验上影响ALS进展。了解小胶质细胞TREM2功能将有助于确定ALS治疗的分子靶点。
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is an aggressive motor neuron degenerative disease characterized by selective loss of both upper and lower motor neurons. The mechanisms underlying disease initiation and progression are poorly understood. The involvement of non-motor neuraxis emphasizes the contribution of glia cells in disease progress. Microglia comprise a unique subset of glial cells and are the principal immune cells in the central nervous system (CNS). Triggering receptor expressed on myeloid cell 2 (TREM2) is a surface receptor that, within the CNS, is exclusively expressed on microglia and plays crucial roles in microglial proliferation, migration, activation, metabolism, and phagocytosis. Genetic evidence has linked TREM2 to neurodegenerative diseases including ALS, but its function in ALS pathogenesis is largely unknown. In this review, we summarize how microglial activation, with a specific focus on TREM2 function, affects ALS progression clinically and experimentally. Understanding microglial TREM2 function will help pinpoint the molecular target for ALS treatment.
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