Using Small Molecules to Dissect Non-apoptotic Programmed Cell Death: Necroptosis, Ferroptosis, and Pyroptosis

Chembiochem. 2015 Dec;16(18):2557-61. doi: 10.1002/cbic.201500422. Epub 2015 Oct 16.

Abstract

Genetically programmed cell death is a universal and fundamental cellular process in multicellular organisms. Apoptosis and necroptosis, two common forms of programmed cell death, play vital roles in maintenance of homeostasis in metazoans. Dysfunction of the regulatory machinery of these processes can lead to carcinogenesis or autoimmune diseases. Inappropriate death of essential cells can lead to organ dysfunction or even death; ischemia-reperfusion injury and neurodegenerative disorders are examples of this. Recently, novel forms of non-apoptotic programmed cell death have been identified. Although these forms of cell death play significant roles in both physiological and pathological conditions, the detailed molecular mechanisms underlying them are still poorly understood. Here, we discuss progress in using small molecules to dissect three forms of non-apoptotic programmed cell death: necroptosis, ferroptosis, and pyroptosis.

Keywords: cancer; ferroptosis; necroptosis; programmed cell death; pyroptosis; signal transduction.

Publication types

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

MeSH terms

  • Animals
  • Cell Death / drug effects*
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Necrosis
  • Pyroptosis / drug effects
  • Quinoxalines / chemistry
  • Quinoxalines / pharmacology
  • Signal Transduction / drug effects
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology
  • Spiro Compounds / chemistry
  • Spiro Compounds / pharmacology

Substances

  • Quinoxalines
  • Small Molecule Libraries
  • Spiro Compounds
  • liproxstatin-1