中国药理学与毒理学杂志2025，Vol.39Issue(10)：780-789,10.DOI:10.3867/j.issn.1000-3002.2025.08493
靶向NLRP3炎症小体的神经系统疾病候选新药研究进展
Advances in development of new drug candidates targeting NLRP3 inflammasome for neurological disorders
摘要
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.关键词
NLRP3炎症小体/抑制剂/天然产物/神经炎症/神经系统疾病/新药研发Key words
NLRP3 inflammasome/inhibitors/natural products/neuroinflammation/neurological disorders/new drug research分类
药学引用本文复制引用
张宝丹,唐婧姝,彭英..靶向NLRP3炎症小体的神经系统疾病候选新药研究进展[J].中国药理学与毒理学杂志,2025,39(10):780-789,10.基金项目
国家自然科学基金(82430113) （82430113）
国家自然科学基金(82373861) （82373861）
北京市自然科学基金(7242206) （7242206）
中国医学科学院医学与健康科技创新工程(2021-I2M-1-028) （2021-I2M-1-028）
中国医学科学院医学与健康科技创新工程(2022-I2M-1-014) National Natural Science Foundation of China(82430113) （2022-I2M-1-014）
National Natural Science Foundation of China(82373861) （82373861）
Beijing Natural Science Foundation(7242206) （7242206）
Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-1-028) （2021-I2M-1-028）
and Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2022-I2M-1-014) （2022-I2M-1-014）
