FDA-approved disulfiram inhibits the NLRP3 inflammasome by regulating NLRP3 palmitoylation.
Cell Rep
; 43(8): 114609, 2024 Aug 27.
Article
en En
| MEDLINE
| ID: mdl-39116210
ABSTRACT
The NLRP3 inflammasome is dysregulated in autoinflammatory disorders caused by inherited mutations and contributes to the pathogenesis of several chronic inflammatory diseases. In this study, we discovered that disulfiram, a safe US Food and Drug Administration (FDA)-approved drug, specifically inhibits the NLRP3 inflammasome but not the NLRC4 or AIM2 inflammasomes. Disulfiram suppresses caspase-1 activation, ASC speck formation, and pyroptosis induced by several stimuli that activate NLRP3. Mechanistically, NLRP3 is palmitoylated at cysteine 126, a modification required for its localization to the trans-Golgi network and inflammasome activation, which was inhibited by disulfiram. Administration of disulfiram to animals inhibited the NLRP3, but not NLRC4, inflammasome in vivo. Our study uncovers a mechanism by which disulfiram targets NLRP3 and provides a rationale for using a safe FDA-approved drug for the treatment of NLRP3-associated inflammatory diseases.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
United States Food and Drug Administration
/
Disulfiram
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Lipoilación
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Inflamasomas
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Proteína con Dominio Pirina 3 de la Familia NLR
Límite:
Animals
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Humans
País/Región como asunto:
America do norte
Idioma:
En
Revista:
Cell Rep
Año:
2024
Tipo del documento:
Article