Zhang CY, Liu S, Sui YX, Yang M. Nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 inflammasome: From action mechanism to therapeutic target in clinical trials. World J Gastrointest Oncol 2025; 17(2): 100094 [PMID: PMC11756006 DOI: 10.4251/wjgo.v17.i2.100094]
Corresponding Author of This Article
Ming Yang, PhD, Assistant Professor, Department of Surgery, University of Connecticut, School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, United States. minyang@uchc.edu
Research Domain of This Article
Immunology
Article-Type of This Article
Editorial
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Oncol. Feb 15, 2025; 17(2): 100094 Published online Feb 15, 2025. doi: 10.4251/wjgo.v17.i2.100094
Nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 inflammasome: From action mechanism to therapeutic target in clinical trials
Chun-Ye Zhang, Shuai Liu, Yu-Xiang Sui, Ming Yang
Chun-Ye Zhang, Bond Life Sciences Center, University of Missouri, Columbia, MO 65212, United States
Shuai Liu, The First Affiliated Hospital, Zhejiang University, Hangzhou 310006, Zhejiang Province, China
Yu-Xiang Sui, School of Life Science, Shanxi Normal University, Linfen 041004, Shanxi Province, China
Ming Yang, Department of Surgery, University of Connecticut, School of Medicine, Farmington, CT 06030, United States
Author contributions: Zhang CY, Liu S, Sui YX, and Yang M designed the study, collected the data and wrote, revised, and finalized the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ming Yang, PhD, Assistant Professor, Department of Surgery, University of Connecticut, School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, United States. minyang@uchc.edu
Received: August 7, 2024 Revised: October 23, 2024 Accepted: November 5, 2024 Published online: February 15, 2025 Processing time: 164 Days and 6.1 Hours
Abstract
The nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome is a critical modulator in inflammatory disease. Activation and mutation of NLRP3 can cause severe inflammation in diseases such as chronic infantile neurologic cutaneous and articular syndrome, Muckle-Wells syndrome, and familial cold autoinflammatory syndrome 1. To date, a great effort has been made to decode the underlying mechanisms of NLRP3 activation. The priming and activation of NLRP3 drive the maturation and release of active interleukin (IL)-18 and IL-1β to cause inflammation and pyroptosis, which can significantly trigger many diseases including inflammatory diseases, immune disorders, metabolic diseases, and neurodegenerative diseases. The investigation of NLRP3 as a therapeutic target for disease treatment is a hot topic in both preclinical studies and clinical trials. Developing potent NLRP3 inhibitors and downstream IL-1 inhibitors attracts wide-spectrum attention in both research and pharmaceutical fields. In this minireview, we first updated the molecular mechanisms involved in NLRP3 inflammasome activation and the associated downstream signaling pathways. We then reviewed the molecular and cellular pathways of NLRP3 in many diseases, including obesity, diabetes, and other metabolic diseases. In addition, we briefly reviewed the roles of NLRP3 in cancer growth and relative immune checkpoint therapy. Finally, clinical trials with treatments targeting NLRP3 and its downstream signaling pathways were summarized.
Core Tip: The nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome plays a pivotal role in many diseases such as inflammatory diseases, metabolic disorders, and neurodegenerative diseases. The investigation of NLRP3 as a therapeutic target is involved in many preclinical studies and clinical trials. Among these studies, NLRP3 inhibitors and downstream interleukin-1 inhibitors attract wide-spectrum attention. In addition, NLRP3 activation also impacts cancer development and immunotherapy, serving as a potential therapeutic target for cancer treatment.
