4.5 Review

Pyroptosis in stroke-new insights into disease mechanisms and therapeutic strategies

Journal

JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
Volume 77, Issue 4, Pages 511-529

Publisher

SPRINGER
DOI: 10.1007/s13105-021-00817-w

Keywords

Stroke; Pyroptosis; Caspase; Inflammasomes; Therapeutic target

Funding

  1. National Science and Technology Major Project of the Ministry of Science and Technology of China [2016ZX09101031, 2019ZX09301-134]
  2. China Pharmaceutical University Double First-Class Construction Technology Innovation Team Project [CPU2018GY23, CPU2018GY24]
  3. China Pharmaceutical University Double First-Class Construction Graduate Education and Teaching Project [JGYB201909]

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Stroke is a common disease with high mortality and disability worldwide. Pyroptosis plays a crucial role in ischemic or hemorrhagic brain tissue, and the relationship between inflammation and stroke is increasingly recognized.
Stroke is a common disease with high mortality and disability worldwide. Different forms of cell deaths, including apoptosis and necrosis, occur in ischemic or hemorrhagic brain tissue, among which pyroptosis, a newly discovered inflammation-related programmed cell death, is generally divided into two main pathways, the canonical inflammasome pathway and the non-canonical inflammasome pathway. Caspase-mediated pyroptosis requires the assembly of inflammasomes such as NLRP3, which leads to the release of inflammatory cytokines IL-1 beta and IL-18 through the pores formed in the plasma membrane by GSDMD followed by neuroinflammation. Recently, pyroptosis and its relationship with inflammation have attracted more and more attention in the study of cerebral ischemia or hemorrhage. In addition, many inhibitors of pyroptosis targeting caspase, NLRP3, and the upstream pathway have been found to reduce brain tissue damage after stroke. In this review, we mainly introduce the pathology of stroke, the molecular mechanism, and process of pyroptosis, as well as the pivotal roles of pyroptosis in stroke, in order to provide new insights for the treatment of stroke.

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