Understanding the involvement of innate immunity and the Nrf2-NLRP3 axis on mitochondrial health in Parkinson's disease

Shruti Rajan, Kamatham Pushpa Tryphena, Sabiya Khan, Lalitkumar Vora*, Saurabh Srivastava*, Shashi Bala Singh, Dharmendra Kumar Khatri*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

18 Citations (Scopus)

Abstract

Parkinson's disease (PD), a multifactorial movement disorder, is interlinked with numerous molecular pathways, including neuroinflammation, which is a critical factor in the development and progression of PD. Microglia play a central role in driving neuroinflammation through activation and overexpression of the M1 phenotype, which has a significant impact on mitochondria. Multiple regulators converge together, and among these, the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes have been implicated in transmitting inflammatory and deleterious components to the mitochondria. Nuclear factor erythroid 2–related factor 2 (Nrf2) regulates the NLRP3 inflammasome and acts as the saviour of the mitochondria. Together, the NLRP3-Nrf2 axis functions in regulating mitochondrial function in the case of PD. It regulates fundamental processes such as oxidative stress, mitochondrial respiratory function, and mitochondrial dynamics. In this review, we discuss the contributions that a variety of miRNAs make to the regulation of the NLRP3 inflammasome and Nrf2, which can be used to target this important axis and contribute to the preservation of mitochondrial integrity. This axis may prove to be a crucial target for extending the lives of Parkinson's patients by deferring neuroinflammatory damage to mitochondria.

Original languageEnglish
Article number101915
Number of pages13
JournalAgeing Research Reviews
Volume87
Early online date22 Mar 2023
DOIs
Publication statusPublished - Jun 2023

Keywords

  • Innate immunity
  • Mitochondria
  • Neuroinflammation
  • NLRP3
  • Nrf2
  • Parkinson's disease
  • Parkinson’s disease

ASJC Scopus subject areas

  • Neurology
  • Ageing
  • Molecular Biology
  • Biochemistry
  • Biotechnology

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