An overview of disease models for NLRP3 inflammasome over-activation

ABSTRACT

Introduction: Inflammatory reactions, including those mediated by the NLRP3 inflammasome, maintain the body’s homeostasis by removing pathogens, repairing damaged tissues, and adapting to stressed environments. However, uncontrolled activation of the NLRP3 inflammasome tends to cause various diseases using different mechanisms. Recently, many inhibitors of the NLRP3 inflammasome have been reported and many are being developed. In order to assess their efficacy, specificity, and mechanism of action, the screening process of inhibitors requires various types of cell and animal models of NLRP3-associated diseases.

Areas covered: In the following review, the authors give an overview of the cell and animal models that have been used during the research and development of various inhibitors of the NLRP3 inflammasome.

Expert opinion: There are many NLRP3 inflammasome inhibitors, but most of the inhibitors have poor specificity and often influence other inflammatory pathways. The potential risk for cross-reaction is high; therefore, the development of highly specific inhibitors is essential. The selection of appropriate cell and animal models, and combined use of different models for the evaluation of these inhibitors can help to clarify the target specificity and therapeutic effects, which is beneficial for the development and application of drugs targeting the NLRP3 inflammasome.

KEYWORDS:

• NLRP3 inflammasome
• disease models
• inhibitor screening
• drug discovery
• inflammatory diseases

Article Highlights

• The most comprehensive and up-to-date overview of disease models for NLRP3 inflammasome over-activation.

• Both cellular and animal models were included and their use in NLRP3 targeted drug discovery.

• 3.Strategies for high specific NLRP3 inhibitor development were provided.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

T Jin is supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB29030104), the National Natural Science Fund (Grant No.: 31870731 and U1732109) as well as the Fundamental Research Funds for the Central Universities. A Zahid is supported by a CAS-TWAS President Fellowship. J Tao is supported by the National Natural Science Foundation of China (81771774), the Natural Science Foundation of Anhui Province (1708085MH191), and the Anhui Key Research and Development Foundation (201904a07020103).