Recent insights into the molecular mechanisms of the NLRP3 inflammasome activation
UMass Chan AffiliationsDepartment of Medicine, Division of Infectious Diseases and Immunology
Document TypeJournal Article
Cellular and Molecular Physiology
Immunology and Infectious Disease
MetadataShow full item record
AbstractInflammasomes are high-molecular-weight protein complexes that are formed in the cytosolic compartment in response to danger- or pathogen-associated molecular patterns. These complexes enable activation of an inflammatory protease caspase-1, leading to a cell death process called pyroptosis and to proteolytic cleavage and release of pro-inflammatory cytokines interleukin (IL)-1beta and IL-18. Along with caspase-1, inflammasome components include an adaptor protein, ASC, and a sensor protein, which triggers the inflammasome assembly in response to a danger signal. The inflammasome sensor proteins are pattern recognition receptors belonging either to the NOD-like receptor (NLR) or to the AIM2-like receptor family. While the molecular agonists that induce inflammasome formation by AIM2 and by several other NLRs have been identified, it is not well understood how the NLR family member NLRP3 is activated. Given that NLRP3 activation is relevant to a range of human pathological conditions, significant attempts are being made to elucidate the molecular mechanism of this process. In this review, we summarize the current knowledge on the molecular events that lead to activation of the NLRP3 inflammasome in response to a range of K (+) efflux-inducing danger signals. We also comment on the reported involvement of cytosolic Ca (2+) fluxes on NLRP3 activation. We outline the recent advances in research on the physiological and pharmacological mechanisms of regulation of NLRP3 responses, and we point to several open questions regarding the current model of NLRP3 activation.
Próchnicki T, Mangan MS, Latz E. Recent insights into the molecular mechanisms of the NLRP3 inflammasome activation. F1000Res. 2016 Jun 22;5:F1000 Faculty Rev-1469. doi: 10.12688/f1000research.8614.1. PMID: 27508077; PMCID: PMC4963208. Link to article on publisher's site