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FDA-approved Disulfiram Inhibits the NLRP3 Inflammasome

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 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 the 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.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: Jie Xu

LAB HEAD: Jie Xu

PROVIDER: PXD054126 | Pride | 2024-07-25

REPOSITORIES: Pride

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			Action	DRS
	PRF_F_2021_G_NUNE_538_51281_51290_1.raw	Raw
	PRF_F_2021_G_NUNE_538_51281_51290_1_8.msf	Msf
	PRF_F_2021_G_NUNE_538_51281_51290_2.raw	Raw
	PRF_F_2021_G_NUNE_538_51281_51290_3.raw	Raw
	PRF_F_2021_G_NUNE_538_51281_51290_4.raw	Raw

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