Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.36 (caspase-1)
 6,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Development of the acute and chronic inflammatory responses known as gout and pseudogout are associated with the deposition of monosodium urate (MSU) or calcium pyrophosphate dihydrate (CPPD) crystals, respectively, in joints and periarticular tissues. Although MSU crystals were first identified as the aetiological agent of gout in the eighteenth century and more recently as a 'danger signal' released from dying cells, little is known about the molecular mechanisms underlying MSU- or CPPD-induced inflammation. Here we show that MSU and CPPD engage the caspase-1-activating NALP3 (also called cryopyrin) inflammasome, resulting in the production of active interleukin (IL)-1beta and IL-18. Macrophages from mice deficient in various components of the inflammasome such as caspase-1, ASC and NALP3 are defective in crystal-induced IL-1beta activation. Moreover, an impaired neutrophil influx is found in an in vivo model of crystal-induced peritonitis in inflammasome-deficient mice or mice deficient in the IL-1beta receptor (IL-1R). These findings provide insight into the molecular processes underlying the inflammatory conditions of gout and pseudogout, and further support a pivotal role of the inflammasome in several autoinflammatory diseases.
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PMID:Gout-associated uric acid crystals activate the NALP3 inflammasome. 1640 89

NLRP3 inflammasome activation and IL-1beta secretion have recently emerged as a central mechanism in the pathogenesis of disease. Genetically defined syndromes like cryopyrin-associated periodic syndromes (CAPS, cryopyrinopathies) and familial Mediterranean fever (FMF) or diseases associated with NLRP3 activation by danger signals like gout, pseudogout, Alzheimer's disease or type 2 diabetes are included in this group of diseases. The contribution of anakinra, a recombinant, nonglycosylated human IL-1 receptor antagonist, in both the identification and treatment of such syndromes was considerable. Recently, rilonacept, a long-acting IL-1 receptor fusion protein, and canakinumab, a fully humanized anti-IL-1beta monoclonal antibody, have been developed, with the intention to further extent IL-1beta inhibition treatment strategies to a broader spectrum of disorders beyond the characterized autoinflammatory syndromes, offering a more favorable administration profile. On the other hand, the developed caspase-1 inhibitors, even though effective in experimental models, were not proven efficient in the treatment of inflammatory diseases.
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PMID:Targeting IL-1beta in disease; the expanding role of NLRP3 inflammasome. 2049 14