Activation of the executioner caspases-3 and -7 promotes microglial pyroptosis in models of multiple sclerosis.

ABSTRACT:

Background

Pyroptosis is a type of proinflammatory regulated cell death (RCD) in which caspase-1 proteolytically cleaves gasdermin D (GSDMD) to yield a cytotoxic pore-forming protein. Recent studies have suggested that additional cell death pathways may interact with GSDMD under certain circumstances to execute pyroptosis. Microglia/macrophages in the central nervous system (CNS) undergo GSDMD-associated pyroptosis in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) but the contribution of other cell death pathways to this phenomenon is unknown. Herein, we tested the hypothesis that multiple RCD pathways underlie microglial pyroptosis in the context of neuroinflammation.

Methods

A siRNA screen of genes with known RCD functions was

SUBMITTER: McKenzie BA 

PROVIDER: S-EPMC7456507 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature