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NLRP3 Inhibitors as Potential Therapeutic Agents for Treatment of Inflammatory Bowel Disease

Perera, APP ORCID: 0000-0002-3674-9940, Kunde, D ORCID: 0000-0002-6513-032X and Eri, R ORCID: 0000-0003-1688-8043 2018 , 'NLRP3 Inhibitors as Potential Therapeutic Agents for Treatment of Inflammatory Bowel Disease' , Current Pharmaceutical Design, vol. 23, no. 16 , pp. 2321-2327 , doi: 10.2174/1381612823666170201162414.

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Abstract

Background: Inflammatory bowel disease (IBD) is a group of intestinal disorders characterised bychronic relapsing inflammation of the small intestine and colon. IBD manifests as either ulcerative colitis orCrohn’s disease and increases the risk of developing colorectal cancer.Methods: Here, we have reviewed current treatment regimen for IBD utilising anti-inflammatory drugs, immunesystem suppressors and antibiotics or a combination of these. However, these therapeutics lead to a number ofadverse effects, remission or significant non-responsiveness creating an urgent need to develop potent drugs withnovel mechanisms of action for IBD.Results: The inflammasome is a multiprotein complex that assembles to a key innate immune system signallingplatform and is involved in the pathogenesis of inflammatory and autoimmune diseases. A number of investigationsshow that the NLRP3 inflammasome recognizes microbial and cell stress components and serve as a platformfor caspase-1 activation and pro-inflammatory cytokine IL-1β, IL18 maturation. Although the exact aetiologyof IBD is unknown, uncontrolled NLRP3 Inflammasome activation has shown to play a major role in thechronic intestinal inflammation and mature IL-1β and IL18 are consistently associated with increased colitis andcolitis associated colorectal cancer development.Conclusion: In this review, we discuss the experimental NLRP3 inhibitors that have been investigated in IBDexperimental models. The potential mechanism of action of these inhibitors such as inhibiting NF-κB activationand decreasing mitochondrial reactive oxygen species are discussed in detail. We further expand the controversialrole of NLRP3 in IBD and future issues that might arise from the long term use of NLRP3 inhibitors in IBD therapy.

Item Type: Article
Authors/Creators:Perera, APP and Kunde, D and Eri, R
Keywords: inflammatory bowel disease, NLRP3 inflammasome, NLRP3 inhibitors, chronic colitis, colorectal cancer, interleukin-1 beta, interleukin-18
Journal or Publication Title: Current Pharmaceutical Design
Publisher: Bentham Science Publ Ltd
ISSN: 1381-6128
DOI / ID Number: 10.2174/1381612823666170201162414
Copyright Information:

© 2017 Bentham Science Publishers

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