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Although its activity is essential to fight infection and support tissue homeostasis, the inflammasome complex, which consists of the danger sensor NLRP3, the adaptor apoptosis-associated speck-like protein containing a CARD (ASC; also known as PYCARD), caspase-1 and probably other regulatory proteins, also bears considerable potential for detrimental inflammation, as observed in human conditions such as gout, heart attack, stroke and Alzheimer's disease. Thus, multi-layered regulatory networks are required to ensure the fine balance between rapid responsiveness versus erroneous activation (sufficient and temporally restricted versus excessive and chronic activity) of the inflammasome. These involve multiple activation, secretion and cell death pathways, as well as modulation of the subcellular localization of NLRP3, and its structure and activity, owing to post-translational modification by other cellular proteins. Here, we discuss the exciting progress that has recently been made in deciphering the regulation of the NLRP3 inflammasome. Additionally, we highlight open questions and describe areas of research that warrant further exploration to obtain a more comprehensive molecular and cellular understanding of the NLRP3 inflammasome.<\/jats:p>","DOI":"10.1242\/jcs.248344","type":"journal-article","created":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T21:10:29Z","timestamp":1607029829000},"source":"Crossref","is-referenced-by-count":86,"title":["Recent insights into the regulatory networks of NLRP3 inflammasome activation"],"prefix":"10.1242","volume":"133","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8627-7056","authenticated-orcid":false,"given":"Alexander N. R.","family":"Weber","sequence":"first","affiliation":[{"name":"Interfaculty Institute for Cell Biology 1 , Department of Immunology , , Auf der Morgenstelle 15, 72076 T\u00fcbingen , Germany"},{"name":"University of T\u00fcbingen 1 , Department of Immunology , , Auf der Morgenstelle 15, 72076 T\u00fcbingen , Germany"},{"name":"iFIT \u2013 Cluster of Excellence (EXC 2180) \u2018Image-Guided and Functionally Instructed Tumor Therapies\u2019, University Hospital T\u00fcbingen - Internal Medicine VIII, Otfried-M\u00fcller-Str. 14, 72076 T\u00fcbingen 2 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zs\u00f3fia A.","family":"Bittner","sequence":"additional","affiliation":[{"name":"Interfaculty Institute for Cell Biology 1 , Department of Immunology , , Auf der Morgenstelle 15, 72076 T\u00fcbingen , Germany"},{"name":"University of T\u00fcbingen 1 , Department of Immunology , , Auf der Morgenstelle 15, 72076 T\u00fcbingen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangeetha","family":"Shankar","sequence":"additional","affiliation":[{"name":"Interfaculty Institute for Cell Biology 1 , Department of Immunology , , Auf der Morgenstelle 15, 72076 T\u00fcbingen , Germany"},{"name":"University of T\u00fcbingen 1 , Department of Immunology , , Auf der Morgenstelle 15, 72076 T\u00fcbingen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Interfaculty Institute for Cell Biology 1 , Department of Immunology , , Auf der Morgenstelle 15, 72076 T\u00fcbingen , Germany"},{"name":"University of T\u00fcbingen 1 , Department of Immunology , , Auf der Morgenstelle 15, 72076 T\u00fcbingen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzu-Hsuan","family":"Chang","sequence":"additional","affiliation":[{"name":"Interfaculty Institute for Cell Biology 1 , Department of Immunology , , Auf der Morgenstelle 15, 72076 T\u00fcbingen , Germany"},{"name":"University of T\u00fcbingen 1 , Department of Immunology , , Auf der Morgenstelle 15, 72076 T\u00fcbingen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengchuan","family":"Jin","sequence":"additional","affiliation":[{"name":"University of Science and Technology of China 3 Division of Life Sciences and Medicine , , Hefei, Anhui 230026 \u2008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Tapia-Abell\u00e1n","sequence":"additional","affiliation":[{"name":"Interfaculty Institute for Cell Biology 1 , Department of Immunology , , Auf der Morgenstelle 15, 72076 T\u00fcbingen , Germany"},{"name":"University of T\u00fcbingen 1 , Department of Immunology , , Auf der Morgenstelle 15, 72076 T\u00fcbingen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2020,12,3]]},"reference":[{"key":"2024061319084856200_JCS248344C1","doi-asserted-by":"publisher","first-page":"2573","DOI":"10.1016\/S0140-6736(15)61153-9","article-title":"Anti-inflammatory therapies in myocardial infarction","volume":"385","author":"Abbate","year":"2015","journal-title":"Lancet"},{"key":"2024061319084856200_JCS248344C2","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/S1074-7613(04)00046-9","article-title":"NALP3 forms an IL-1\u03b2-processing inflammasome with increased activity in muckle-wells autoinflammatory disorder","volume":"20","author":"Agostini","year":"2004","journal-title":"Immunity"},{"key":"2024061319084856200_JCS248344C3","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1016\/j.jaci.2017.03.041","article-title":"Bruton tyrosine kinase inhibition: clinical relevance beyond B cells","volume":"140","author":"Banoth","year":"2017","journal-title":"J. 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