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Molecular Mechanism of the Protective Effects of M2 Microglia on Neurons: A Review Focused on Exosomes and Secretory Proteins

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Abstract

Microglia, as innate immune cells in the brain, closely monitor changes in the internal environment and participate in the maintenance of homeostasis in the central nervous system (CNS). Microglia can be polarized to the M1 or M2 phenotype in response to various stimuli in vivo or in vitro, affecting the functions of peripheral neurons. M2 microglia have attracted increasing attention in recent years owing to their beneficial effects on various diseases and injuries of the CNS, such as traumatic brain injury, stroke, Alzheimer’s disease and multiple sclerosis. They exert neuroprotective effects by various mechanisms, e.g., suppressing inflammation, promoting the degradation of misfolded and aggregated proteins, promoting neurite growth, enhancing neurogenesis, inhibiting autophagy and apoptosis, promoting myelination, maintaining blood–brain barrier integrity, and enhancing phagocytic activity.This review summarizes the molecular mechanisms by which M2 microglia exert protective effects on neurons and provides a reference for the selection of therapeutic targets for CNS diseases.

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Funding

This work was supported by the National Natural Science Foundation of China (Grant No.31,870,335); the Natural Science Foundation of Gansu Provincial Department of Science and Technology (Grant No.20JR5RA344); the Health Industry Planning Project of Gansu Provincial (Grant No.GSWSKY2021-017); Science and Technology Planing Project of Chengguan District of Lanzhou City (Grant No.2021-9-3); the “Cuiying Technology Innovation” Planning Project of Lanzhou University Second Hospital (CY2021-MS-B01); the Lanzhou Science and Technology Development Guiding Plan Project (Grant No.2019-ZD-51) and Cuiying Graduate Supervisor Applicant Training Program of Lanzhou University Second Hospital (Grant No.201,802).

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Authors and Affiliations

  1. Department of Neurology, Lanzhou University Second Hospital, 730030, Lanzhou, Gansu, China

    Miao Chai, Juan Gao, Wei Chen, Qionghui Wu, Ying Dong, He Wang, Deyi Chen, Xin Gao, Ruixin Li, Tianfei Ma & Zhenchang Zhang

  2. Institute of Genetics, School of Basic Medical Sciences, Lanzhou University, 730030, Lanzhou, Gansu, China

    Gang Su

  3. NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, 730000, Lanzhou, China

    Yonghong Li

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  1. Miao Chai
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Contributions

Miao Chai, Ying Dong, and He Wang had the idea for the review and collected the articles. The first draft of the manuscript was written by Miao Chai.Juan Gao, Wei Chen, Qionghui Wu, Deyi Chen, Yonghong Li, Xin Gao, Ruixin Li, and Tianfei Ma contributed to revision of the review. Gang Su and Zhenchang Zhang edited the review and performed proofreading and final editing. All authors have read and approved the final manuscript.

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Correspondence to Zhenchang Zhang.

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Miao Chai and Gang Su contributed equally to this work.

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Chai, M., Su, G., Gao, J. et al. Molecular Mechanism of the Protective Effects of M2 Microglia on Neurons: A Review Focused on Exosomes and Secretory Proteins. Neurochem Res 47, 3556–3564 (2022). https://doi.org/10.1007/s11064-022-03760-4

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