Chemical Modulation of Gasdermin-Mediated Pyroptosis and Therapeutic Potential

J Mol Biol. 2022 Feb 28;434(4):167183. doi: 10.1016/j.jmb.2021.167183. Epub 2021 Aug 3.

Abstract

Pyroptosis, a lytic form of programmed cell death, both stimulates effective immune responses and causes tissue damage. Gasdermin (GSDM) proteins are a family of pore-forming executors of pyroptosis. While the most-studied member, GSDMD, exerts critical functions in inflammasome biology, emerging evidence demonstrates potential broad relevance for GSDM-mediated pyroptosis across diverse pathologies. In this review, we describe GSDM biology, outline conditions where inflammasomes and GSDM-mediated pyroptosis represent rational therapeutic targets, and delineate strategies to manipulate these central immunologic processes for the treatment of human disease.

Keywords: anti-tumor immunity; immunogenic cell death; inflammasome; inflammasomopathy; pore-forming protein.

Publication types

  • Review

MeSH terms

  • Humans
  • Inflammasomes* / metabolism
  • Molecular Targeted Therapy*
  • Phosphate-Binding Proteins* / metabolism
  • Pore Forming Cytotoxic Proteins* / metabolism
  • Pyroptosis* / drug effects

Substances

  • GSDMD protein, human
  • Inflammasomes
  • Phosphate-Binding Proteins
  • Pore Forming Cytotoxic Proteins