Fiery Cell Death: Pyroptosis in the Central Nervous System

Brienne A McKenzie; Vishva M Dixit; Christopher Power

doi:10.1016/j.tins.2019.11.005

Fiery Cell Death: Pyroptosis in the Central Nervous System

Trends Neurosci. 2020 Jan;43(1):55-73. doi: 10.1016/j.tins.2019.11.005. Epub 2019 Dec 13.

Authors

Brienne A McKenzie¹, Vishva M Dixit², Christopher Power³

Affiliations

¹ Department of Medical Microbiology and Immunology, University of Alberta, Edmonton AB, Canada; Department of Medicine, Neuroscience and Mental Health Institute, University of Alberta, Edmonton AB, Canada.
² Department of Physiological Chemistry, Genentech, South San Francisco, CA, USA.
³ Department of Medicine, Neuroscience and Mental Health Institute, University of Alberta, Edmonton AB, Canada. Electronic address: chris.power@ualberta.ca.

PMID: 31843293
DOI: 10.1016/j.tins.2019.11.005

Abstract

Pyroptosis ('fiery death') is an inflammatory type of regulated cell death (RCD), which occurs downstream of inflammasome activation. Pyroptosis is mediated directly by the recently identified family of pore-forming proteins known as gasdermins, the best characterized of which is gasdermin D (GSDMD). Recent investigations implicate pyroptosis in the pathogenesis of multiple neurological diseases. In this review, we discuss molecular mechanisms that drive pyroptosis, evidence for pyroptosis within the CNS, and emerging therapeutic strategies for its inhibition in the context of neurological disease.

Keywords: caspase; central nervous system; glia; inflammasome; neuron; pyroptosis; regulated cell death.

Publication types

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

MeSH terms

Central Nervous System* / cytology
Central Nervous System* / pathology
Humans
Inflammasomes / metabolism
Intracellular Signaling Peptides and Proteins
Nervous System Diseases* / pathology
Nervous System Diseases* / therapy
Phosphate-Binding Proteins
Pyroptosis*

Substances

Inflammasomes
Intracellular Signaling Peptides and Proteins
Phosphate-Binding Proteins