연구성과 홍보

Cell Mol Immunol. 2025 Jun;22(6):563-596.

Title : Updated insights into the molecular networks for NLRP3 inflammasome activation

Authors : Seungwha Paik#1,2,3,4, Jin Kyung Kim#5, Hyo Jung Shin2,6,7, Eun-Jin Park1,2, In Soo Kim2,4,8, Eun-Kyeong Jo9,10,11*

Affiliations :

1Department of Microbiology, Chungnam National University College of Medicine, Daejeon, Republic of Korea.

2Department of Medical Science, Chungnam National University College of Medicine, Daejeon, Republic of Korea.

3System Network Inflammation Control Research Center, Chungnam National University College of Medicine, Daejeon, Republic of Korea.

4Biomedical Research Institute, Chungnam National University Hospital, Daejeon, Republic of Korea.

5Department of Microbiology, Keimyung University School of Medicine, Daegu, Republic of Korea.

6Department of Biochemistry and Cell Biology, Eulji University School of Medicine, Daejeon, Republic of Korea.

7Brain Research Institute, Chungnam National University College of Medicine, Daejeon, Republic of Korea.

8Department of Pharmacology, Chungnam National University College of Medicine, Daejeon, Republic of Korea.

9Department of Microbiology, Chungnam National University College of Medicine, Daejeon, Republic of Korea.

10Department of Medical Science, Chungnam National University College of Medicine, Daejeon, Republic of Korea.

11Biomedical Research Institute, Chungnam National University Hospital, Daejeon, Republic of Korea.

DOI: 10.1038/s41423-025-01284-9.

Abstract :

Over the past decade, significant advances have been made in our understanding of how NACHT-, leucine-rich-repeat-, and pyrin domain-containing protein 3 (NLRP3) inflammasomes are activated. These findings provide detailed insights into the transcriptional and posttranslational regulatory processes, the structural-functional relationship of the activation processes, and the spatiotemporal dynamics of NLRP3 activation. Notably, the multifaceted mechanisms underlying the licensing of NLRP3 inflammasome activation constitute a focal point of intense research. Extensive research has revealed the interactions of NLRP3 and its inflammasome components with partner molecules in terms of positive and negative regulation. In this Review, we provide the current understanding of the complex molecular networks that play pivotal roles in regulating NLRP3 inflammasome priming, licensing and assembly. In addition, we highlight the intricate and interconnected mechanisms involved in the activation of the NLRP3 inflammasome and the associated regulatory pathways. Furthermore, we discuss recent advances in the development of therapeutic strategies targeting the NLRP3 inflammasome to identify potential therapeutics for NLRP3-associated inflammatory diseases. As research continues to uncover the intricacies of the molecular networks governing NLRP3 activation, novel approaches for therapeutic interventions against NLRP3-related pathologies are emerging.