However, the aberrant activation of the NLRP3 inflammasome has been linked with several inflammatory disorders, which include cryopyrin-associated periodic syndromes, Alzheimer's disease, diabetes, and atherosclerosis.
Gain-of-function mutations in NLRP3 in CAPS patients lead to activation of the cryopyrin inflammasome, resulting in the inappropriate release of inflammatory cytokines including IL-1β and CAPS-related inflammatory symptoms.
These results identify wild-type NLRP3 as the molecular target of MCC950/CRID3 and show that CAPS-related NLRP3 mutants escape efficient MCC950/CRID3 inhibition.
The cryopyrin associated periodic syndrome (CAPS), the hyper IgD syndrome (HIDS) and the TNF receptor-associated periodic syndrome (TRAPS), are autoinflammatory conditions associated with mutations in the NLRP3, MVK and TNFRSF1A genes, respectively.
With respect to NLRP3 mosaicism in CAPS, a prospective longitudinal study on the variant genotype, its allele frequency and its tissue distribution (along with a comprehensive clinical phenotype) would provide better understanding of NLRP3 mosaicism, resulting in more appropriate patient care and genetic counseling.
Cryopyrin-associated periodic syndrome (CAPS) is a hereditary autoinflammatory syndrome caused by mutations in <i>NLRP3</i> (encoding cryopyrin), which presents with fever, fatigue and arthralgia.
Mutated NLRP3 assembles a hyperactive inflammasome, which causes excessive secretion of interleukin (IL)-1β and IL-18 and, ultimately, a spectrum of autoinflammatory disorders known as cryopyrinopathies of which neonatal-onset multisystem inflammatory disease (NOMID) is the most severe phenotype.
CAPS are associated with GOF mutations in the NLRP3 inflammasome and activation of IL-1ß leading to episodes of fever, cutaneous, musculoskeletal, articular, ocular, and neurological symptoms.
Contrary to the NLRP3 mutations described in cryopyrin-associated periodic syndrome, FMF-associated MEFV mutations do not lead to a constitutive activation of Pyrin.
Remarkably, single TLR4 stimulation is sufficient to activate massive, GSDMD-mediated IL-1β secretion in monocytes from patients affected by Cryopyrin Associated Periodic Syndrome (CAPS), an autoinflammatory disease linked to NLRP3 mutations.
Cryopyrin associated periodic syndromes (CAPS) comprise a spectrum of autoinflammatory disorders of varying severity caused by mutations in the NLRP3 gene.
It specifically belongs to the cryopyrin-associated periodic syndromes (CAPSs) in which there is a mutation in the NLRP<sub>3</sub> (NLR family pyrin domain containing 3) gene that leads to overproduction of IL-1β, the source of the multisystem inflammatory symptoms.
Gain-of-function missense mutations in NLRP3 result in a group of autoinflammatory diseases collectively known as the cryopyrin-associated periodic syndromes (CAPS).
Cryopyrin-associated periodic syndromes (CAPS) result from gain-of-function mutations in the NLRP3 gene, which causes excessive release of interleukin-1β (IL-1β) and systemic inflammation.
Importantly, treatment with CY-09 shows remarkable therapeutic effects on mouse models of cryopyrin-associated autoinflammatory syndrome (CAPS) and type 2 diabetes.
Gain-of-function mutations of <i>NLRP3</i> result in abnormal activation of the NLRP3 inflammasome, and cause the autosomal dominant systemic autoinflammatory disease spectrum, termed cryopyrin-associated periodic syndromes (CAPS).
CAPS are associated with gain-of-function mutations in the NLRP3 inflammasome, a multiprotein complex critical for the activation of IL-1ß, and are characterized by episodes of fever, urticaria-like rash, musculoskeletal, ocular, and neurological symptoms.
Cryopyrin-associated periodic syndromes (CAPS) is a rare group of autoinflammatory disorders that includes familial cold autoinflammatory syndrome or FCAS, Muckle-wells syndrome or MWS, and neonatal-onset multisystem inflammatory disease or NOMID.