NLRP3 inflammasome

NLRP3 inflammasome

What is the relevance of NLRP3 inflammasome to specific autoinflammatory syndromes

The gene CIAS1 on chromosome 1 encodes for the NLRP3 (or NALP3) protein, previously called cryopyrin . NLRP3 is a member of the nucleotide-binding oligomerization domain-leucine-rich repeat (NOD-LRR) protein family. It consists of a pyrin domain (PYD), a NOD (also called NACHT), and an LRR domain. NLRP3 is primarily found in neutrophils and monocytes and is an intracellular sensor of pathogens and danger signals (pathogen-/damage-associated molecular patterns; Overview of the Immune Response, Inflammation, and Autoimmunity). Upon stimulation, NLRP3 interacts with adaptor proteins ASC and Cardinal, forming a multiprotein complex called the NLRP3 inflammasome . ASC contains a PYD and a caspase activation and recruitment domain (CARD), whereas Cardinal contains a function to find (FIIND) domain and a CARD domain. The PYD of NLRP3 interacts with PYD of ASC, and the LRR domain of NLRP3 interacts with FIIND of Cardinal. This activates both CARDs, which then interact with CARD on procaspase 1, therein activating it to caspase 1 (also called the IL-β converting enzyme). Caspase 1 can activate pro-IL-1β to be released as the proinflammatory cytokine IL-1β. Genetic mutations in several of these proteins are associated with specific autoinflammatory syndromes.

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