2. Academic Validation
  3. Disulfiram suppresses NLRP3 inflammasome activation to treat peritoneal and gouty inflammation

Disulfiram suppresses NLRP3 inflammasome activation to treat peritoneal and gouty inflammation

  • Free Radic Biol Med. 2020 May 20;152:8-17. doi: 10.1016/j.freeradbiomed.2020.03.007.
Wenmin Deng 1,  Zhongjin Yang 1,  Hu Yue 1,  Yitao Ou 1,  Wenhui Hu 2,  Ping Sun 3
Affiliations

Affiliations

  • 1 Key Laboratory of Molecular Target & Clinical Pharmacology and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 511436, China.
  • 2 Key Laboratory of Molecular Target & Clinical Pharmacology and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 511436, China. Electronic address: huwenhui@gzhmu.edu.cn.
  • 3 Key Laboratory of Molecular Target & Clinical Pharmacology and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 511436, China. Electronic address: sun_ping@gzhmu.edu.cn.
PMID: 32151746 DOI: 10.1016/j.freeradbiomed.2020.03.007
Abstract

The NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome plays a vital role in mediating the innate immune system. Its aberrant activation contributes to the progression of several devastating diseases such as acute peritonitis, acute liver injury, sepsis, gout, and Others. However, the medications targeting NLRP3 inflammasome are not available in the clinic. Reusing marketed drugs, which have been already proved to possess good pharmacokinetic profiles and safety, is a strategy to develop new NLRP3 inflammasome inhibitors for clinical trials. In this study, we identified disulfiram (DSF), an old marketed drug as a treatment for alcoholism, could effectively inhibit NLRP3 inflammasome activation and suppress pyroptotic cell death. DSF prevented lysosomal Cathepsin B releasing into the cytoplasm, which in turn inactivated the NLRP3 inflammasome. DSF also reduced mitochondrial-independent ROS production. More importantly, treatment with DSF showed remarkable therapeutic effects on the LPS-induced peritoneal inflammation and MSU-induced gouty inflammation. This study provides a potential pharmacological approach to treating NLRP3-driven diseases and a tool to study NLRP3 biology.

Keywords

Cathepsin B; Disulfiram; Lysosome; NLRP3 inflammasome; ROS.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z