Targeting pyroptosis to regulate ischemic stroke injury: Molecular mechanisms and preclinical evidences

Abstract

Stroke is one of the leading causes of death worldwide with limited therapies. After ischemic stroke occurs, a robust sterile inflammatory response happens and lasts for days and determines neurological prognosis. Pyroptosis is an inflammatory programmed cell death characterized by cleavage of pore-forming proteins gasdermins as a result of activating caspases and inflammasomes. It has morphological characteristics of rapid plasma-membrane rupture and release of proinflammatory intracellular contents as well as cytokines. Recent researches implicate pyroptosis involvement in the pathogenesis of ischemic stroke and inhibition of pyroptosis attenuates ischemic brain injury. In this review, we discussed molecular mechanisms of pyroptosis, evidences for pyroptosis involvement in different kinds of the central nervous system cells, as well as potential inhibitors for intervention of pyroptosis. Based on the review, we hypothesize the feasibility of therapeutic strategies targeting pyroptosis in the context of ischemic stroke.

Keywords: Gasdermins; Inflammasomes; Ischemic stroke; Pyroptosis.