NLRP3 inflammasomes: A potential target to improve mitochondrial biogenesis in Parkinson's disease

Eur J Pharmacol. 2022 Nov 5:934:175300. doi: 10.1016/j.ejphar.2022.175300. Epub 2022 Sep 24.

Abstract

Parkinson's disease (PD) is a common neurodegenerative condition for which no approved treatment exists to prevent collective neuronal death. There is ample evidence that mitochondrial dysfunction, reactive oxygen species (ROS), and associated caspase activity underlie the pathology observed. Neurons rely on mitochondrial activity since they have such high energy consumption. Therefore, it is not surprising that mitochondrial alterations favour neuronal degeneration. In particular, mitochondrial dysregulation contributes to PD, based on the observation that mitochondrial toxins can cause parkinsonism in humans and animal models. Also, it is known that inflammatory cytokine-mediated neuroinflammation is the key pathogenic mechanism in neuronal loss. In recent years, the research has focussed on mitochondria being the platform for nucleotide-binding oligomerization domain-like receptors 3 (NLRP3) inflammasome activation. Mitochondrial dysfunction and NLRP3 activation are emerging as critical players in inducing and sustaining neuroinflammation. Moreover, mitochondrial-derived ROS and mitochondrial DNA (mtDNA) could serve as the priming signal for forming inflammasome complexes responsible for the activation, maturation, and release of pro-inflammatory cytokines, including interleukin-1(IL-1) and interleukin-18 (IL-18). The current review takes a more comprehensive approach to elucidating the link between mitochondrial dysfunction and aberrant NLRP3 activation in PD. In addition, we focus on some inhibitors of NLRP3 inflammatory pathways to alleviate the progression of PD.

Keywords: Cytokines; Mitochondria; NLRP3; Neuroinflammation; Parkinson's disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Caspases
  • DNA, Mitochondrial
  • Humans
  • Inflammasomes* / metabolism
  • Interleukin-1
  • Interleukin-18
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Nucleotides
  • Organelle Biogenesis
  • Parkinson Disease* / metabolism
  • Reactive Oxygen Species / metabolism

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Interleukin-18
  • Reactive Oxygen Species
  • DNA, Mitochondrial
  • Interleukin-1
  • Nucleotides
  • Caspases