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

Inflamm Res. 2023 Mar;72(3):443-462. doi: 10.1007/s00011-022-01676-x. Epub 2023 Jan 4.

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.

Keywords: Autophagy; Microglia; Neuroinflammation; Phagocytosis; α-Synuclein.

Publication types

  • Review

MeSH terms

  • Autophagy
  • Humans
  • Inflammasomes / metabolism
  • Microglia / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Neurodegenerative Diseases* / metabolism
  • Neurodegenerative Diseases* / pathology
  • Neuroinflammatory Diseases
  • Parkinson Disease* / genetics
  • Parkinson Disease* / metabolism
  • Parkinson Disease* / pathology
  • Phagocytosis
  • alpha-Synuclein / genetics
  • alpha-Synuclein / metabolism

Substances

  • alpha-Synuclein
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • SNCA protein, human