Journal Article (Review Article)

DZNE-2025-00999

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The expanding role of the NLRP3 inflammasome from periodic fevers to therapeutic targets.

Weber, A. N. R. ; McManus, R. M.DZNE* ; Hornung, V. ; Geyer, M. ; Kuemmerle-Deschner, J. B. ; Latz, E.Extern*

2025
Springer Nature Limited London

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Please use a persistent id in citations: doi:10.1038/s41590-025-02230-7

Abstract: Understanding and treating inflammation has proven a formidable challenge. The initiator and central motor of inflammation, the protein NLRP3, is an innate immune sentinel and nonspecific sensor of cellular perturbation. A wide array of inflammatory triggers prompts the formation of an NLRP3 'inflammasome' complex, leading to inflammatory interleukin-1 family cytokine release and pyroptotic cell death. Since gain-of-function mutations in NLRP3 were demonstrated to cause a rare autoinflammatory disease termed cryopyrin-associated periodic syndrome, NLRP3 has emerged as key mediator of inflammation in mouse models for many common diseases, including atherosclerosis, Alzheimer's disease and gout. But even though small-molecule NLRP3 modulators have entered clinical development, many aspects of NLRP3 activation and regulation in humans remain relatively unclear. This Review summarizes the current understanding of the molecular mechanisms that drive NLRP3 inflammasome activation and regulation, and discusses emerging targeting strategies. Understanding these processes can guide precision medicine approaches aimed at mitigating NLRP3-driven pathologies.

Keyword(s): NLR Family, Pyrin Domain-Containing 3 Protein: metabolism (MeSH) ; NLR Family, Pyrin Domain-Containing 3 Protein: genetics (MeSH) ; NLR Family, Pyrin Domain-Containing 3 Protein: immunology (MeSH) ; Humans (MeSH) ; Inflammasomes: metabolism (MeSH) ; Inflammasomes: immunology (MeSH) ; Animals (MeSH) ; Cryopyrin-Associated Periodic Syndromes: immunology (MeSH) ; Cryopyrin-Associated Periodic Syndromes: drug therapy (MeSH) ; Cryopyrin-Associated Periodic Syndromes: genetics (MeSH) ; Mice (MeSH) ; Inflammation: immunology (MeSH) ; NLR Family, Pyrin Domain-Containing 3 Protein ; Inflammasomes ; NLRP3 protein, human

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Contributing Institute(s):

1. Translational Neuroimmunology (AG McManus)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Nature ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 30 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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