Focus on the role of mitochondria in NLRP3 inflammasome activation: A prospective target for the treatment of ischemic stroke (Review)

Int J Mol Med. 2022 Jun;49(6):74. doi: 10.3892/ijmm.2022.5130. Epub 2022 Apr 8.

Abstract

Post‑ischemic neuroinflammation induced by the innate local immune response is a major pathophysiological feature of cerebral ischemic stroke, which remains the leading cause of mortality and disability worldwide. NLR family pyrin domain containing (NLRP)3 inflammasome crucially mediates post‑ischemic inflammatory responses via its priming, activation and interleukin‑1β release during hypoxic‑ischemic brain damage. Mitochondrial dysfunctions are among the main hallmarks of several brain diseases, including ischemic stroke. In the present review, focus was addressed on the role of mitochondria in cerebral ischemic stroke while keeping NLRP3 inflammasome as a link. Under ischemia and hypoxia, mitochondria are capable of controlling NLRP3 inflammasome‑mediated neuroinflammation through mitochondrial released contents, mitochondrial localization and mitochondrial related proteins. Thus, inflammasome and mitochondria may be attractive targets to treat ischemic stroke as well as the several drugs that target the process of mitochondrial function to treat cerebral ischemic stroke. At present, certain drugs have already been studied in clinical trials.

Keywords: NLR family pyrin domain containing 3 inflammasome; ischemic stroke; mitochondria; neuroinflammation; treatment.

Publication types

  • Review

MeSH terms

  • Humans
  • Inflammasomes / metabolism
  • Ischemic Stroke*
  • Mitochondria / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Prospective Studies
  • Stroke* / metabolism

Substances

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

Grants and funding

The present study was supported by the National Natural Science Foundation of China (grant nos. 82074211 and 82160828) and the Research and Innovation Project of Graduate (grant nos. 2020YJSS208, YJSKC-20201021 and ZXYCXLX201902).