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Role of α-synuclein in microglia: autophagy and phagocytosis balance neuroinflammation in Parkinson’s disease

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Abstract

Background

Parkinson’s disease (PD) is the second most common neurodegenerative disease, and is characterized by accumulation of α-synuclein (α-syn). Neuroinflammation driven by microglia is an important pathological manifestation of PD. α-Syn is a crucial marker of PD, and its accumulation leads to microglia M1-like phenotype polarization, activation of NLRP3 inflammasomes, and impaired autophagy and phagocytosis in microglia. Autophagy of microglia is related to degradation of α-syn and NLRP3 inflammasome blockage to relieve neuroinflammation. Microglial autophagy and phagocytosis of released α-syn or fragments from apoptotic neurons maintain homeostasis in the brain. A variety of PD-related genes such as LRRK2, GBA and DJ-1 also contribute to this stability process.

Objectives

Further studies are needed to determine how α-syn works in microglia.

Methods

A keyword-based search was performed using the PubMed database for published articles.

Conclusion

In this review, we discuss the interaction between microglia and α-syn in PD pathogenesis and the possible mechanism of microglial autophagy and phagocytosis in α-syn clearance and inhibition of neuroinflammation. This may provide a novel insight into treatment of PD.

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Acknowledgements

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Funding

This work was supported by grants from the National Natural Science Foundation of China (82071420), Jiangsu Provincial Key R&D Program (BE2018658), Suzhou Technology Development Programme (SLJ2021010), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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Authors and Affiliations

  1. Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China

    Qian-Kun Lv, **ao-Yu Yao, Fen Wang & Chun-Feng Liu

  2. Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, 215123, China

    Qian-Kun Lv, Kang-**n Tao, **ao-Bo Wang, **ao-Yu Yao, Meng-Zhu Pang, Fen Wang & Chun-Feng Liu

  3. Department of Neurology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, China

    Jun-Yi Liu

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  1. Qian-Kun Lv
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  7. Fen Wang
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  8. Chun-Feng Liu
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Contributions

QL wrote the manuscript; KT contributed to figure generation; XW contributed to table generation; XY, MP and JL contributed to conception of the study; FW and CL was involved in the project design and supervision, and manuscript revision. All authors read and approved the final manuscript.

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Correspondence to Fen Wang or Chun-Feng Liu.

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Lv, QK., Tao, KX., Wang, XB. et al. Role of α-synuclein in microglia: autophagy and phagocytosis balance neuroinflammation in Parkinson’s disease. Inflamm. Res. 72, 443–462 (2023). https://doi.org/10.1007/s00011-022-01676-x

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