Parkinson's disease: connecting mitochondria to inflammasomes

Trends Immunol. 2022 Nov;43(11):877-885. doi: 10.1016/j.it.2022.09.010. Epub 2022 Oct 11.

Abstract

Activated microglia foster a neurotoxic, inflammatory environment in the mammalian central nervous system (CNS) that drives the pathology of neurodegenerative diseases including Parkinson's disease (PD). Moreover, mitochondrial fission promotes microglial inflammatory responses in vitro. Given that the NLRP3 inflammasome and mitochondria are central regulators of both inflammation and PD, we explore potential functions for the NLRP3 inflammasome and mitochondrial dynamics in PD. Specifically, we propose that inducible microglial mitochondrial fission can promote NLRP3-dependent neuroinflammation in hereditary and idiopathic PD. Further in-depth exploration of this topic can prompt valuable discoveries of the underlying molecular mechanisms of PD neuroinflammation, identify novel candidate anti-inflammatory therapeutics for PD, and ideally provide better outcomes for PD patients.

Keywords: NLRP3; Parkinson's; inflammasome; inflammation; neurodegeneration; neuroinflammation.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / pathology
  • Humans
  • Inflammasomes* / metabolism
  • Mammals
  • Microglia
  • Mitochondria
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Parkinson Disease* / pathology

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein