Therapeutic strategies targeting the NLRP3‑mediated inflammatory response and pyroptosis in cerebral ischemia/reperfusion injury (Review)

Mol Med Rep. 2024 Mar;29(3):46. doi: 10.3892/mmr.2024.13170. Epub 2024 Jan 26.

Abstract

Ischemic stroke poses a major threat to human health. Therefore, the molecular mechanisms of cerebral ischemia/reperfusion injury (CIRI) need to be further clarified, and the associated treatment approaches require exploration. The NOD‑like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome serves an important role in causing CIRI, and its activation exacerbates the underlying injury. Activation of the NLRP3 inflammasome triggers the maturation and production of the inflammatory molecules IL‑1β and IL‑18, as well as gasdermin‑D‑mediated pyroptosis and CIRI damage. Thus, the NLRP3 inflammasome may be a viable target for the treatment of CIRI. In the present review, the mechanisms of the NLRP3 inflammasome in the intense inflammatory response and pyroptosis induced by CIRI are discussed, and the therapeutic strategies that target the NLRP3‑mediated inflammatory response and pyroptosis in CIRI are summarized. At present, certain drugs have already been studied, highlighting future therapeutic perspectives.

Keywords: CIRI; NLRP3 inflammasome; inflammation; pyroptosis; therapeutic target.

Publication types

  • Review

MeSH terms

  • Brain Ischemia* / drug therapy
  • Brain Ischemia* / metabolism
  • Humans
  • Inflammasomes / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Pyroptosis
  • Reperfusion Injury* / drug therapy
  • Reperfusion Injury* / metabolism

Substances

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

Grants and funding

This work was supported by the National Natural Science Foundation of China (grant no. 82101410) and the Medicine and Health Science and Technology Development Plan Project of Shandong (grant no. 202101040805).