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The identity and function of microglia in neurodegeneration

Abstract

The predominant type of immune cell in the brain is the microglia, a type of tissue-resident macrophage. In a variety of neurodegenerative settings, microglia alter their transcriptional profile, morphology and function in similar ways; thus, these activated cells have been called ‘degeneration- or disease-associated microglia’ (DAM). These activated microglia can perform different functions and exert both positive effects and negative effects in different mouse disease models. In humans, mutations in genes expressed in microglia are linked to various neurodegenerative diseases. Here we provide an overview of the common microglial response to neurodegeneration and key contributing pathways; delineate the multifaceted functions of activated microglia spanning various diseases; and discuss insights from the study of human disease-associated genes. We argue that strong evidence from both mouse models and human genetics causally links the function of activated microglia to neurodegeneration.

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Fig. 1: DAM are a unique population present in various neuropathologies.
Fig. 2: DAM respond to both extracellular insults and intraneuronal insults.
Fig. 3: Certain genetic alterations that affect mainly microglia or both microglia and neurons are linked to neurodegeneration.
Fig. 4: Possible non–mutually exclusive explanations for discrepancies between human genetics and mouse model experiments.

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Song, W.M., Colonna, M. The identity and function of microglia in neurodegeneration. Nat Immunol 19, 1048–1058 (2018). https://doi.org/10.1038/s41590-018-0212-1

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