Mechanisms and Therapeutic Regulation of Pyroptosis in Inflammatory Diseases and Cancer

Int J Mol Sci. 2020 Feb 20;21(4):1456. doi: 10.3390/ijms21041456.

Abstract

Programmed Cell Death (PCD) is considered to be a pathological form of cell death when mediated by an intracellular program and it balances cell death with survival of normal cells. Pyroptosis, a type of PCD, is induced by the inflammatory caspase cleavage of gasdermin D (GSDMD) and apoptotic caspase cleavage of gasdermin E (GSDME). This review aims to summarize the latest molecular mechanisms about pyroptosis mediated by pore-forming GSDMD and GSDME proteins that permeabilize plasma and mitochondrial membrane activating pyroptosis and apoptosis. We also discuss the potentiality of pyroptosis as a therapeutic target in human diseases. Blockade of pyroptosis by compounds can treat inflammatory disease and pyroptosis activation contributes to cancer therapy.

Keywords: GSDMD; GSDME; cancer therapy; inflammatory disease; pyroptosis.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Membrane / metabolism
  • Cell Membrane / pathology
  • Cell Membrane Permeability
  • Humans
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / therapy
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mitochondrial Membranes / metabolism
  • Mitochondrial Membranes / pathology
  • Neoplasm Proteins / metabolism*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Phosphate-Binding Proteins / metabolism*
  • Pyroptosis*
  • Receptors, Estrogen / metabolism*

Substances

  • GSDMD protein, human
  • GSDME protein, human
  • Intracellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • Phosphate-Binding Proteins
  • Receptors, Estrogen