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      NLRP3 Inflammasome and Inflammatory Diseases

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          Abstract

          Almost all human diseases are strongly associated with inflammation, and a deep understanding of the exact mechanism is helpful for treatment. The NLRP3 inflammasome composed of the NLRP3 protein, procaspase-1, and ASC plays a vital role in regulating inflammation. In this review, NLRP3 regulation and activation, its proinflammatory role in inflammatory diseases, interactions with autophagy, and targeted therapeutic approaches in inflammatory diseases will be summarized.

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          The NLRP3 inflammasome: molecular activation and regulation to therapeutics

          Karen V. Swanson, Meng Deng, Jenny P.-Y. Ting (2019)
          NLRP3 (NACHT, LRR and PYD domains-containing protein 3) is an intracellular sensor that detects a broad range of microbial motifs, endogenous danger signals and environmental irritants, resulting in the formation and activation of the NLRP3 inflammasome. Assembly of the NLRP3 inflammasome leads to caspase-1-dependent release of the proinflammatory cytokines, IL-1β and IL-18, as well as to gasdermin D-mediated pyroptotic cell death. Recent studies have revealed new regulators of the NLRP3 inflammasome, including new interacting or regulatory proteins, metabolic pathways and a regulatory mitochondrial hub. In this Review, we present the molecular, cell biological and biochemical basis of NLRP3 activation and regulation, and describe how this mechanistic understanding is leading to potential therapeutics that target the NLRP3 inflammasome.
          Article 0 comments Cited 1492 times – based on 0 reviews     Review now
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            Targeting the NLRP3 inflammasome in inflammatory diseases

            Edward Olhava, Matthew S J Mangan, William Roush … (2018)
            Article 0 comments Cited 486 times – based on 0 reviews     Review now
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              NLRP3 inflammasome and its inhibitors: a review

              Bo-zong Shao, Zhe-Qi Xu, Bin-ze Han … (2015)
              Inflammasomes are newly recognized, vital players in innate immunity. The best characterized is the NLRP3 inflammasome, so-called because the NLRP3 protein in the complex belongs to the family of nucleotide-binding and oligomerization domain-like receptors (NLRs) and is also known as “pyrin domain-containing protein 3”. The NLRP3 inflammasome is associated with onset and progression of various diseases, including metabolic disorders, multiple sclerosis, inflammatory bowel disease, cryopyrin-associated periodic fever syndrome, as well as other auto-immune and auto-inflammatory diseases. Several NLRP3 inflammasome inhibitors have been described, some of which show promise in the clinic. The present review will describe the structure and mechanisms of activation of the NLRP3 inflammasome, its association with various auto-immune and auto-inflammatory diseases, and the state of research into NLRP3 inflammasome inhibitors.
              Article 0 comments Cited 333 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Li Li:
                ORCID: https://orcid.org/0000-0003-1790-0147
                Journal
                Journal ID (nlm-ta): Oxid Med Cell Longev
                Journal ID (iso-abbrev): Oxid Med Cell Longev
                Journal ID (publisher-id): OMCL
                Title: Oxidative Medicine and Cellular Longevity
                Publisher: Hindawi
                ISSN (Print): 1942-0900
                ISSN (Electronic): 1942-0994
                Publication date Collection: 2020
                Publication date (Electronic): 17 February 2020
                Volume: 2020
                Electronic Location Identifier: 4063562
                Affiliations
                1Department of Hepatobiliary Surgery, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, China
                2Department of Ophthalmology, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, China
                Author notes

                Guest Editor: Marco Cordani

                Author information
                https://orcid.org/0000-0002-0490-466X
                https://orcid.org/0000-0001-5739-6104
                https://orcid.org/0000-0002-6855-0207
                https://orcid.org/0000-0001-9023-5580
                https://orcid.org/0000-0001-6122-6853
                https://orcid.org/0000-0002-7674-698X
                https://orcid.org/0000-0003-4281-5534
                https://orcid.org/0000-0002-8389-5289
                https://orcid.org/0000-0003-1790-0147
                Article
                DOI: 10.1155/2020/4063562
                PMC ID: 7049400
                PubMed ID: 32148650
                SO-VID: fcca8bbc-fe2d-4162-beb5-958f913a2527
                Copyright © Copyright © 2020 Zheng Wang et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 6 December 2019
                Date revision received : 14 January 2020
                Date accepted : 17 January 2020
                Funding
                Funded by: Science and Technology Innovation
                Funded by: National Natural Science Foundation of China
                Award ID: 81872008
                Categories
                Subject: Review Article

                ScienceOpen disciplines: Molecular medicine
                Data availability:
                ScienceOpen disciplines: Molecular medicine

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