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Review
. 2021 Sep 24:15:742065.
doi: 10.3389/fnins.2021.742065. eCollection 2021.

Microglia in Neuroinflammation and Neurodegeneration: From Understanding to Therapy

Luca Muzio  1 , Alice Viotti  1 , Gianvito Martino  1
Affiliations
Review

Microglia in Neuroinflammation and Neurodegeneration: From Understanding to Therapy

Luca Muzio et al. Front Neurosci. .

Abstract

Microglia are the resident macrophages of the central nervous system (CNS) acting as the first line of defense in the brain by phagocytosing harmful pathogens and cellular debris. Microglia emerge from early erythromyeloid progenitors of the yolk sac and enter the developing brain before the establishment of a fully mature blood-brain barrier. In physiological conditions, during brain development, microglia contribute to CNS homeostasis by supporting cell proliferation of neural precursors. In post-natal life, such cells contribute to preserving the integrity of neuronal circuits by sculpting synapses. After a CNS injury, microglia change their morphology and down-regulate those genes supporting homeostatic functions. However, it is still unclear whether such changes are accompanied by molecular and functional modifications that might contribute to the pathological process. While comprehensive transcriptome analyses at the single-cell level have identified specific gene perturbations occurring in the "pathological" microglia, still the precise protective/detrimental role of microglia in neurological disorders is far from being fully elucidated. In this review, the results so far obtained regarding the role of microglia in neurodegenerative disorders will be discussed. There is solid and sound evidence suggesting that regulating microglia functions during disease pathology might represent a strategy to develop future therapies aimed at counteracting brain degeneration in multiple sclerosis, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.

Keywords: Alzheimer’ disease; Parkinson’s disease; amyotrophic lateral sclerosis; brain aging; microglia; multiple sclerosis; neurodegeneration; neuroinflammation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
In the pathological context, microglia undergo morphologic and phenotypic changes upon activation. Disease-Associated Microglia (DAMs), Injury-Responsive Microglia (IRMs), and aged microglia represent different activation states, each characterized by a specific transcriptional signature.
FIGURE 2
FIGURE 2
During pathological processes, microglial activation is involved in the disease progression, residing in a chronic state of activation.
See this image and copyright information in PMC

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