Open AccessThe NLRP3 inflammasome: molecular activation and regulation to therapeutics
Author(s) -
Karen V. Swanson,
Meng Deng,
Jenny P.-Y. Ting
Publication year - 2019
Publication title -
nature reviews. immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 20.529
H-Index - 390
eISSN - 1474-1741
pISSN - 1474-1733
DOI - 10.1038/s41577-019-0165-0
Subject(s) - inflammasome , pyrin domain , microbiology and biotechnology , intracellular , nod , chemistry , caspase 1 , nalp3 , pyroptosis , programmed cell death , biology , receptor , biochemistry , apoptosis , gene
NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) is an intracellular sensor that detects a broad range of microbial motifs, endogenous danger signals and environmental irritants, resulting in the formation and activation of the NLRP3 inflammasome. Assembly of the NLRP3 inflammasome leads to caspase 1-dependent release of the pro-inflammatory cytokines IL-1β and IL-18, as well as to gasdermin D-mediated pyroptotic cell death. Recent studies have revealed new regulators of the NLRP3 inflammasome, including new interacting or regulatory proteins, metabolic pathways and a regulatory mitochondrial hub. In this Review, we present the molecular, cell biological and biochemical bases of NLRP3 activation and regulation and describe how this mechanistic understanding is leading to potential therapeutics that target the NLRP3 inflammasome.