Advances in development of new drug candidates targeting NLRP3 inflammasome for neurological disorders
10.3867/j.issn.1000-3002.2025.08493
- VernacularTitle:靶向NLRP3炎症小体的神经系统疾病候选新药研究进展
- Author:
Baodan ZHANG
1
;
Jingshu TANG
1
;
Ying PENG
1
Author Information
1. 中国医学科学院北京协和医学院药物研究所,北京 100050
- Publication Type:Journal Article
- Keywords:
NLRP3 inflammasome;
inhibitors;
natural products;
neuroinflammation;
neurological disorders;
new drug research
- From:
Chinese Journal of Pharmacology and Toxicology
2025;39(10):780-789
- CountryChina
- Language:Chinese
-
Abstract:
Excessive activation of the NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome drives neuronal injury in neurological disorders.The NLRP3 inflammasome complex comprises NLRP3,apoptosis-associated speck-like protein containing a CARD(ASC)and cysteine aspartic acid specific protease-1(Caspase-1).Upon activation through canonical or non-canonical pathways,this complex triggers the release of IL-1β/IL-18 and induces pyroptosis.Clinical evidence has pointed to the co-localization of ASC with amyloid β-protein(Aβ)plaques in the brains of Alzheimer disease(AD)patients,specific upregulation of NLRP3 in monocytes of multiple sclerosis patients,and a positive correlation between serum NLRP3 levels and infarct volume in stroke patients,suggesting that NLRP3 inflammasome can be used as a critical therapeutic target.This review summa-rizes the pathological roles of the NLRP3 inflammasome and recent advances in candidate therapeutics.The targeting strategies include direct inhibitors,upstream regulators and downstream blockers.However,clinical translation of small-molecule inhibitors faces challenges due to the blood-brain barrier,inade-quate disease modeling and off-target toxicity concerns.Emerging solutions include nanocarrier systems,Al-assisted drug design and novel target exploration.Future research should use stem cell-derived organoid models and molecular subtyping approaches to advance precision medicine and facilitate clinical translation.
