Pyroptosis, and its Role in Central Nervous System Disease

J Mol Biol. 2022 Feb 28;434(4):167379. doi: 10.1016/j.jmb.2021.167379. Epub 2021 Nov 25.

Abstract

Pyroptosis is an inflammatory form of cell death executed by transmembrane pore-forming proteins known as gasdermins and can be activated in an inflammasome-dependent or -independent manner. Inflammasome-dependent pyroptosis is triggered in response to pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) and has emerged as an important player in the pathogenesis of multiple inflammatory diseases, mainly by releasing inflammatory contents. More recently, numerous studies have revealed the intricate mechanisms of pyroptosis and its role in the development of neuroinflammation in central nervous system (CNS) diseases. In this review, we summarize current understandings of the molecular and regulatory mechanisms of pyroptosis. In addition, we discuss how pyroptosis can drive different forms of neurological diseases and new promising therapeutic strategies targeting pyroptosis that can be leveraged to treat neuroinflammation.

Keywords: caspase; gasdermins; inflammasomes; neuroinflammation; neurological diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Central Nervous System Diseases*
  • Humans
  • Inflammasomes / metabolism
  • Pyroptosis* / physiology

Substances

  • Inflammasomes