Broad-spectrum inflammasome inhibition by thiomuscimol.

ABSTRACT: Inflammasome formation, arising from pathogen or internal activating signals, is a key step in canonical pyroptosis, a gasdermin-mediated inflammatory cell death. Inhibition of pyroptosis has great clinical relevance due to its involvement in many different disease states. Current inhibitors of pyroptosis either only inhibit the final lytic step, which still allows inflammatory signal release, or only inhibit a single inflammasome, which does not account for inherent redundancy in activation of other inflammatory pathways. Here, we show that thiomuscimol, a structural analog of the lysis inhibitor muscimol, exhibits unique inhibitory activity upstream of plasma membrane rupture. We find that thiomuscimol inhibits inflammasome formation, as well as downstream caspase-1 activation, initiated

SUBMITTER: Anderson MJ 

PROVIDER: S-EPMC11569204 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature