Zhang Hai Yan, Yan Han, Tang Xi Can
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Rd, Shanghai, 201203, China.
Cell Mol Neurobiol. 2008 Feb;28(2):173-83. doi: 10.1007/s10571-007-9163-z. Epub 2007 Jul 27.
The use of acetylcholinesterase inhibitors to decrease the breakdown of the neurotransmitter acetylcholine has been the main symptomatic therapy for mild to moderate Alzheimer's patients, though the etiology of Alzheimer's disease remains unclear and seems to involve multiple factors. Further evidence has indicated that some of these acetylcholinesterase inhibitors also have non-cholinergic functions on the pathogenesis of Alzheimer's disease including the formation and deposition of beta-amyloid. Huperzine A, a potent and reversible inhibitor of acetylcholinesterase that was initially isolated from a Chinese herb, has been found to improve cognitive deficits in a broad range of animal models and has been used for Alzheimer's disease treatment in China. The novel neuroprotective effects of huperzine A might yield beneficial effects in Alzheimer's disease therapy and provide a potential template for the design of new selective and powerful anti-Alzheimer's drugs. The present paper gives an overview on the neuroprotective effects of huperzine A beyond its acetylcholinesterase inhibition. These effects include regulating beta-amyloid precursor protein metabolism, protecting against beta-amyloid-mediated oxidative stress and apoptosis. The structure-function relationship of huperzine A is also discussed.
使用乙酰胆碱酯酶抑制剂来减少神经递质乙酰胆碱的分解，一直是轻度至中度阿尔茨海默病患者的主要对症治疗方法，尽管阿尔茨海默病的病因仍不清楚，且似乎涉及多种因素。进一步的证据表明，其中一些乙酰胆碱酯酶抑制剂在阿尔茨海默病的发病机制上还具有非胆碱能功能，包括β-淀粉样蛋白的形成和沉积。石杉碱甲是一种强效且可逆的乙酰胆碱酯酶抑制剂，最初从一种中草药中分离出来，已发现在多种动物模型中可改善认知缺陷，并在中国被用于治疗阿尔茨海默病。石杉碱甲的新型神经保护作用可能会在阿尔茨海默病治疗中产生有益效果，并为设计新的选择性强效抗阿尔茨海默病药物提供潜在模板。本文概述了石杉碱甲除抑制乙酰胆碱酯酶外的神经保护作用。这些作用包括调节β-淀粉样前体蛋白代谢、抵御β-淀粉样蛋白介导的氧化应激和细胞凋亡。还讨论了石杉碱甲的结构-功能关系。
