期刊
DEVELOPMENTAL NEUROBIOLOGY
卷 82, 期 1, 页码 125-137出版社
WILEY
DOI: 10.1002/dneu.22864
关键词
amyotrophic lateral sclerosis; disease-associated microglia; microglia; TDP-43; TREM2
资金
- National Institutes of Health [R01NS088627, R21AG064159, U19AG069701]
ALS, a motor neuron degenerative disease, involves the activation of glial cells, particularly microglia, with a focus on the role of the surface receptor TREM2. Understanding the function of TREM2 in ALS pathogenesis can help identify potential molecular targets for treatment.
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 nonmotor neuraxis emphasizes the contribution of glial 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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