An overview of disease models for NLRP3 inflammasome over-activation

Expert Opin Drug Discov. 2021 Apr;16(4):429-446. doi: 10.1080/17460441.2021.1844179. Epub 2020 Dec 21.

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; drug discovery; inflammatory diseases; inhibitor screening.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Drug Development
  • Humans
  • Inflammasomes / drug effects*
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human