Journal
FRONTIERS IN PHARMACOLOGY
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2022.780496
Keywords
NLRP3; inflammasome; NAFLD; NASH; therapeutic agents
Categories
Funding
- National Natural Science Foundation [81500675, 82070895, 81671226]
- Research and training funds of School of Basic medical sciences [JCYXYKY202023]
- Open Project Program of the Third Affiliated Hospital of Xinxiang Medical University [KFKTYB202127]
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NAFLD is a common primary liver disease worldwide with no effective treatment currently available. Recent studies suggest that activation of the NLRP3 inflammasome plays a crucial role in the development of NAFLD. Several NLRP3 inflammasome inhibitors have shown promising results in experimental and clinical studies.
Non-alcoholic fatty liver disease (NAFLD) is among the most prevalent primary liver diseases worldwide and can develop into various conditions, ranging from simple steatosis, through non-alcoholic steatohepatitis (NASH), to fibrosis, and eventually cirrhosis and hepatocellular carcinoma. Nevertheless, there is no effective treatment for NAFLD due to the complicated etiology. Recently, activation of the NLPR3 inflammasome has been demonstrated to be a contributing factor in the development of NAFLD, particularly as a modulator of progression from initial hepatic steatosis to NASH. NLRP3 inflammasome, as a caspase-1 activation platform, is critical for processing key pro-inflammatory cytokines and pyroptosis. Various stimuli involved in NAFLD can activate the NLRP3 inflammasome, depending on the diverse cellular stresses that they cause. NLRP3 inflammasome-related inhibitors and agents for NAFLD treatment have been tested and demonstrated positive effects in experimental models. Meanwhile, some drugs have been applied in clinical studies, supporting this therapeutic approach. In this review, we discuss the activation, biological functions, and treatment targeting the NLRP3 inflammasome in the context of NAFLD progression. Specifically, we focus on the different types of therapeutic agents that can inhibit the NLRP3 inflammasome and summarize their pharmacological effectiveness for NAFLD treatment.
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