Spotlight on the NLRP3 inflammasome pathway

Spotlight on the NLRP3 inflammasome pathway

Marine Groslambert,1–5 Bénédicte F Py1–5 1Centre International de Recherche en Infectiologie (CIRI), Université de Lyon, Lyon, France; 2INSERM, U1111, Lyon, France; 3Ecole Normale Supérieure de Lyon, Lyon, France; 4Centre International...

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Autores principales: Groslambert M, Py BF
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2018
Materias:
inflammation
NLRP3
inflammasome
post-translational modifications
Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
Acceso en línea:https://doaj.org/article/74e0c664b46e4fc5b87a4452c8369b92
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spelling oai:doaj.org-article:74e0c664b46e4fc5b87a4452c8369b922021-12-02T05:49:07ZSpotlight on the NLRP3 inflammasome pathway1178-7031https://doaj.org/article/74e0c664b46e4fc5b87a4452c8369b922018-09-01T00:00:00Zhttps://www.dovepress.com/spotlight-on-the-nlrp3-inflammasome-pathway-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Marine Groslambert,1–5 Bénédicte F Py1–5 1Centre International de Recherche en Infectiologie (CIRI), Université de Lyon, Lyon, France; 2INSERM, U1111, Lyon, France; 3Ecole Normale Supérieure de Lyon, Lyon, France; 4Centre International de Recherche en Infectiologie, Université Lyon 1, Lyon, France; 5CNRS, UMR5308, Lyon, France Abstract: Inflammation is triggered by a repertoire of receptors detecting infections and damages. Some of these receptors directly bind microbial ligands, while others recognize endogenous molecules exposed under stress conditions, including infections. Most of these receptors can be engaged by a relatively limited number of stimuli. Differently, NLRP3 acts as a broad sensor of cell homeostasis rupture and can be activated downstream of a plethora of stimuli. NLRP3 then assembles a multiprotein platform resulting in caspase-1 activation, which controls, by direct cleavage, the maturation of cytosolic pro-cytokines including pro-interleukin-1β. In addition, caspase-1 processes cytosolic gasdermin-D and unleashes its pore-forming N-terminal domain, leading to the release of mature cytosolic cytokines and alarmins, as well as pyroptotic cell lysis. Accumulating evidences of the aggravating role of NLRP3-mediated inflammation in various highly prevalent human conditions, including diabetes, neurodegenerative and cardiovascular diseases, raises a huge clinical interest. Nevertheless, the molecular mechanism governing NLRP3 activation remains insufficiently understood. In line with the detrimental consequences of NLRP3 activation illustrated by the aforementioned pathologies, this process is tightly regulated. In this review, we address the current understanding of the control of NLRP3 activity which can be divided into two coordinated processes referred to as priming and activation. In particular, we detail the emerging role of NLRP3 post-translational modifications critical in inflammasome assembly regulation. Keywords: inflammation, NLRP3, inflammasome, post-translational modificationsGroslambert MPy BFDove Medical PressarticleinflammationNLRP3inflammasomepost-translational modificationsPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 11, Pp 359-374 (2018)
institution DOAJ
collection DOAJ
language EN
topic inflammation
NLRP3
inflammasome
post-translational modifications
Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
spellingShingle inflammation
NLRP3
inflammasome
post-translational modifications
Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
Groslambert M
Py BF
Spotlight on the NLRP3 inflammasome pathway
description Marine Groslambert,1–5 Bénédicte F Py1–5 1Centre International de Recherche en Infectiologie (CIRI), Université de Lyon, Lyon, France; 2INSERM, U1111, Lyon, France; 3Ecole Normale Supérieure de Lyon, Lyon, France; 4Centre International de Recherche en Infectiologie, Université Lyon 1, Lyon, France; 5CNRS, UMR5308, Lyon, France Abstract: Inflammation is triggered by a repertoire of receptors detecting infections and damages. Some of these receptors directly bind microbial ligands, while others recognize endogenous molecules exposed under stress conditions, including infections. Most of these receptors can be engaged by a relatively limited number of stimuli. Differently, NLRP3 acts as a broad sensor of cell homeostasis rupture and can be activated downstream of a plethora of stimuli. NLRP3 then assembles a multiprotein platform resulting in caspase-1 activation, which controls, by direct cleavage, the maturation of cytosolic pro-cytokines including pro-interleukin-1β. In addition, caspase-1 processes cytosolic gasdermin-D and unleashes its pore-forming N-terminal domain, leading to the release of mature cytosolic cytokines and alarmins, as well as pyroptotic cell lysis. Accumulating evidences of the aggravating role of NLRP3-mediated inflammation in various highly prevalent human conditions, including diabetes, neurodegenerative and cardiovascular diseases, raises a huge clinical interest. Nevertheless, the molecular mechanism governing NLRP3 activation remains insufficiently understood. In line with the detrimental consequences of NLRP3 activation illustrated by the aforementioned pathologies, this process is tightly regulated. In this review, we address the current understanding of the control of NLRP3 activity which can be divided into two coordinated processes referred to as priming and activation. In particular, we detail the emerging role of NLRP3 post-translational modifications critical in inflammasome assembly regulation. Keywords: inflammation, NLRP3, inflammasome, post-translational modifications
format article
author Groslambert M
Py BF
author_facet Groslambert M
Py BF
author_sort Groslambert M
title Spotlight on the NLRP3 inflammasome pathway
title_short Spotlight on the NLRP3 inflammasome pathway
title_full Spotlight on the NLRP3 inflammasome pathway
title_fullStr Spotlight on the NLRP3 inflammasome pathway
title_full_unstemmed Spotlight on the NLRP3 inflammasome pathway
title_sort spotlight on the nlrp3 inflammasome pathway
publisher Dove Medical Press
publishDate 2018
url https://doaj.org/article/74e0c664b46e4fc5b87a4452c8369b92
work_keys_str_mv AT groslambertm spotlightonthenlrp3inflammasomepathway
AT pybf spotlightonthenlrp3inflammasomepathway
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