2. Academic Validation
  3. The NLRP3 inflammasome: molecular activation and regulation to therapeutics

The NLRP3 inflammasome: molecular activation and regulation to therapeutics

  • Nat Rev Immunol. 2019 Aug;19(8):477-489. doi: 10.1038/s41577-019-0165-0.
Karen V Swanson 1,  Meng Deng 2 3,  Jenny P-Y Ting 4 5 6 7
Affiliations

Affiliations

  • 1 Department of Medicine, Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • 2 Oral and Craniofacial Biomedicine Program, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • 3 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • 4 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. [email protected].
  • 5 Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. [email protected].
  • 6 Institute for Inflammatory Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. [email protected].
  • 7 Center for Translational Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. [email protected].
PMID: 31036962 DOI: 10.1038/s41577-019-0165-0
Abstract

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.

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