Inflammasome inhibition under physiological and pharmacological conditions.

Genes and Immunity
Emily A CaseleyMichael F McDermott

Abstract

Inflammasomes are key regulators of the host response against microbial pathogens, in addition to limiting aberrant responses to sterile insults, as mediated by environmental agents such as toxins or nanoparticles, and also by endogenous danger signals such as monosodium urate, ATP and amyloid-β. To date at least six different inflammasome signalling platforms have been reported (Bauernfeind & Hornung, EMBO Mol Med. 2013;5:814-26; Broz & Dixit, Nat Rev Immunol. 2016;16:407). This review focuses on the complex molecular machinery involved in activation and regulation of the best characterised inflammasome, NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3), and the development of molecular agents to modulate NLRP3 inflammasome function. Activation of the NLRP3 inflammasome induces inflammation via secretion of interleukin-1β (IL-1β) and interleukin-18 (IL-18) proinflammatory cytokines, with orchestration of pyroptotic cell death, to eliminate invading microbial pathogens. This field has gradually moved from an emphasis on monogenic autoinflammatory conditions, such as cryopyrin-associated periodic syndromes (CAPS), to the broad spectrum of innate immune-mediated disease. NLRP3 inflammasome activation is also linked to a ra...Continue Reading

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Citations

Nov 3, 2020·Expert Opinion on Drug Discovery·Hongliang ZhangJinhui Tao
Mar 29, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Vishal Khatri, Ramaswamy Kalyanasundaram
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May 1, 2021·International Journal of Molecular Sciences·Jana Adamcakova, Daniela Mokra
Aug 10, 2021·Frontiers in Physiology·Elena HofmannBong-Sung Kim

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Methods Mentioned

BETA
ubiquitination
electron microscopy
sumoylation
deubiquitination

Clinical Trials Mentioned

NCT03389308
NCT04351100
NCT03534297
NCT03595371
NCT03923140
NCT03528070
NCT03512873
NCT03490708

Software Mentioned

INFEVERS

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