Zu Runru, Lu Hao, Liu Wanting, Shao Simai, Zheng Jiayao, Ying Xiran, Zhou Yangang, Li Zhonghua, Wang Wang, Li Dejuan, Peng Quekun, Ma Huifen, Zhang Zhenqiang, Sun Yiran
Henan Engineering Research Center for Prevention and Treatment of Major Chronic Diseases With Chinese Medicine, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China.
School of Pharmacy, Chengdu Medical College, Chengdu, 610500, PR China.
Mol Neurobiol. 2025 Jun;62(6):7296-7312. doi: 10.1007/s12035-025-04715-w. Epub 2025 Jan 28.
Alzheimer's disease (AD) is a prominent neurodegenerative disorder affecting the central nervous system in the elderly. Current understanding of AD primarily centers on the gradual decline in cognitive and memory functions, believed to be influenced by factors including mitochondrial dysfunction, β-amyloid aggregation, and neuroinflammation. Emerging research indicates that neuroinflammation plays a significant role in the development of AD, with the inflammasome potentially mediating inflammatory responses that contribute to neurodegeneration. Recent studies in AD pathology have identified a novel form of inflammasome referred to as NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome. Pathological alterations closely associated with NLRP3 inflammasome activation have been observed in the brain tissues of AD patients, transgenic mice, and in vitro neurocyte models. Numerous studies have demonstrated the potent neuroprotective properties of natural plant products (NPPs) against NLRP3 inflammasome-mediated AD pathology. This review provides a comprehensive examination of the NLRP3 inflammasome, its involvement in AD pathology, and the mechanisms underlying the therapeutic effects of NPP targeting the NLRP3 inflammasome.
阿尔茨海默病(AD)是一种影响老年人中枢神经系统的突出神经退行性疾病。目前对AD的认识主要集中在认知和记忆功能的逐渐衰退上,据信这受到包括线粒体功能障碍、β-淀粉样蛋白聚集和神经炎症等因素的影响。新兴研究表明,神经炎症在AD的发展中起重要作用,炎性小体可能介导导致神经退行性变的炎症反应。AD病理学的最新研究发现了一种新型炎性小体,称为含NOD样受体吡咯结构域3(NLRP3)炎性小体。在AD患者、转基因小鼠的脑组织以及体外神经细胞模型中,均观察到与NLRP3炎性小体激活密切相关的病理改变。大量研究表明,天然植物产物(NPPs)对NLRP3炎性小体介导的AD病理学具有强大的神经保护作用。本综述全面考察了NLRP3炎性小体、其在AD病理学中的作用以及NPP靶向NLRP3炎性小体的治疗作用机制。