title: Recent insights into the molecular mechanisms of the NLRP3 inflammasome activation.
abstract: Inflammasomes 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)-1β 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.
authors: Institute of Innate Immunity, University Hospital, University of Bonn, Bonn, Germany.
authors: Tomasz
authors: T
authors: Próchnicki
authors: Institute of Innate Immunity, University Hospital, University of Bonn, Bonn, Germany; German Center for Neurodegenerative Diseases, Bonn, Germany.
authors: Matthew S
authors: MS
authors: Mangan
authors: Institute of Innate Immunity, University Hospital, University of Bonn, Bonn, Germany; Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA, USA; German Center for Neurodegenerative Diseases, Bonn, Germany; Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway.
authors: Eicke
authors: E
authors: Latz
keywords: Inflammasome; NLRP3; autoinflammatory disease; pyroptosis