Disease-Associated Microglia: A Universal Immune Sensor of Neurodegeneration

被引：996

作者：

Deczkowska, Aleksandra ^{[1
]}

Keren-Shaul, Hadas ^{[1
,2
]}

Weiner, Assaf ^{[1
]}

Colonna, Marco ^{[3
]}

Schwartz, Michal ^{[4
]}

Amit, Ido ^{[1
]}

机构：

[1] Weizmann Inst Sci, Dept Immunol, Rehovot, Israel

[2] Weizmann Inst Sci, Life Sci Core Facil, Rehovot, Israel

[3] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA

[4] Weizmann Inst Sci, Dept Neurobiol, Rehovot, Israel

来源：

CELL | 2018年 / 173卷 / 05期

基金：

欧洲研究理事会; 以色列科学基金会;

关键词：

AMYOTROPHIC-LATERAL-SCLEROSIS; GENE-EXPRESSION SIGNATURE; ALZHEIMERS-DISEASE; AMYLOID-BETA; MOUSE MODEL; APOLIPOPROTEIN-E; TREM2; DEFICIENCY; BRAIN; ACTIVATION; MICE;

D O I：

10.1016/j.cell.2018.05.003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

A major challenge in the field of neurodegenerative diseases and brain aging is to identify the body's intrinsic mechanism that could sense the central nervous system (CNS) damage early and protect the brain from neurodegeneration. Accumulating evidence suggests that disease-associated microglia (DAM), a recently identified subset of CNS resident macrophages found at sites of neurodegeneration, might play such a protective role. Here, we propose that microglia are endowed with a dedicated sensory mechanism, which includes the Trem2 signaling pathway, to detect damage within the CNS in the form of neurodegeneration-associated molecular patterns (NAMPs). Combining data from transcriptional analysis of DAM at single-cell level and from human genome-wide association studies (GWASs), we discuss potential function of different DAM pathways in the diseased brain and outline how manipulating DAM may create new therapeutic opportunities.

引用

页码：1073 / 1081

页数：9

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