TY  - JOUR
AU  - Weber, Alexander N R
AU  - McManus, Róisín M
AU  - Hornung, Veit
AU  - Geyer, Matthias
AU  - Kuemmerle-Deschner, Jasmin B
AU  - Latz, Eicke
TI  - The expanding role of the NLRP3 inflammasome from periodic fevers to therapeutic targets.
JO  - Nature immunology
VL  - 26
IS  - 9
SN  - 1529-2908
CY  - London
PB  - Springer Nature Limited
M1  - DZNE-2025-00999
SP  - 1453 - 1466
PY  - 2025
AB  - 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.
KW  - NLR Family, Pyrin Domain-Containing 3 Protein: metabolism
KW  - NLR Family, Pyrin Domain-Containing 3 Protein: genetics
KW  - NLR Family, Pyrin Domain-Containing 3 Protein: immunology
KW  - Humans
KW  - Inflammasomes: metabolism
KW  - Inflammasomes: immunology
KW  - Animals
KW  - Cryopyrin-Associated Periodic Syndromes: immunology
KW  - Cryopyrin-Associated Periodic Syndromes: drug therapy
KW  - Cryopyrin-Associated Periodic Syndromes: genetics
KW  - Mice
KW  - Inflammation: immunology
KW  - NLR Family, Pyrin Domain-Containing 3 Protein (NLM Chemicals)
KW  - Inflammasomes (NLM Chemicals)
KW  - NLRP3 protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40826276
DO  - DOI:10.1038/s41590-025-02230-7
UR  - https://pub.dzne.de/record/280916
ER  -