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Beyond inflammasomes: emerging function of gasdermins during apoptosis and NETosis

Kaiwen W Chen1, Benjamin Demarco1, Petr Broz1

  • 1Department of Biochemistry, University of Lausanne, Lausanne, Switzerland.

The EMBO Journal
|December 4, 2019
PubMed

Insights

Programmed cell death, including apoptosis, pyroptosis, and NETosis, involves Gasdermin D (GSDMD). This review explores gasdermin roles in cell death pathways and associated diseases.

Area of Science:

  • Cellular Biology
  • Immunology
  • Molecular Biology

Background:

  • Programmed cell death is crucial for development, homeostasis, and immunity, removing damaged or infected cells.
  • Dysregulation of cell death pathways is linked to diseases like cancer, neurodegeneration, and infections.
  • Apoptosis, pyroptosis, and NETosis were thought to be distinct but show cross-talk, converging on Gasdermin D (GSDMD).

Purpose of the Study:

  • To review recent advancements in gasdermin research.
  • To focus on the role of gasdermins in pyroptosis, NETosis, and apoptosis.
  • To discuss gasdermin activation consequences and controversies surrounding Gasdermin E (GSDME).

Main Methods:

  • Literature review of recent studies on gasdermins.
  • Analysis of cross-talk between apoptosis, pyroptosis, and NETosis.
  • Examination of Gasdermin D (GSDMD) and Gasdermin E (GSDME) functions.

Main Results:

  • Gasdermin D (GSDMD) is a key effector protein converging multiple cell death pathways.
  • Gasdermins play significant roles in pyroptosis, NETosis, and apoptosis.
  • Gasdermin E (GSDME) involvement in pyroptosis and secondary necrosis is under investigation.

Conclusions:

  • Gasdermin proteins are central to programmed cell death execution.
  • Understanding gasdermin function is critical for disease pathogenesis and therapeutic strategies.
  • Further research is needed to clarify Gasdermin E (GSDME) roles and resolve existing controversies.
Keywords:
NETosisapoptosisgasdermininflammasomepyroptosis

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