新型益脑双联体防治阿尔采末病作用及机制研究进展  

Research progress in characterizing multiple-target mechanisms of novel anti-Alzheimer's dimers

作　　者：苏玮[1] 朱龙军[2] 许大平 崔巍[1,3] 张在军[2,3] 胡胜全[1,3] 麦成雄 韩怡凡[1,3] 

机构地区：[1]香港理工大学应用生物与化学技术学系 [2]暨南大学新药研究所,广东广州510632 [3]香港理工大学深圳研究院,广东深圳518057

出　　处：《中国药理学通报》2014年第9期1201-1205,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81202510);香港政府研究基金(No PolyU5610/11M;PolyU5609/09M);香港理工大学研究基金(No G-U952;G-YM32;G-YZ15);香江学者资助项目(No 122870)

摘　　要：阿尔采末病(Alzheimer’s disease,AD)是多因素、多环节机制介导的复杂疾病,"一药多靶位"药物可能是防治AD最有前途的方向。新型益脑双联体[Bis(n)-Cognitin]是本研究小组改造自他克林的高活性抗AD双联体。实验研究表明,Bis(n)-Cognitin可同时作用乙酰胆碱酯酶、β-分泌酶、N-甲基-D-天冬氨酸受体、神经元型一氧化氮合酶等多个AD重要靶标,具有抑制β-淀粉样蛋白神经毒性、阻断神经兴奋性毒性、降低氧化应激和线粒体损伤、改善动物学习记忆能力、在体对抗神经细胞凋亡等作用,极有可能成为未来防治AD的高效药物。Alzheimer＇s disease （ AD ） is a complex disease caused by environmental and genetic factors. Therefore, one-drug-multiple-target compounds represent the most promising pharmacological approaches to preventing and treating this dis-ease. We have previously designed and synthesized bis（ n）-Cog-nitin, novel anti-Alzheimer＇s dimers derived from tacrine. Bis （ n）-Cognitin have been proven to act on multiple important AD targets, including acetylcholinesterase, β-secretase, N-methyl-D-aspartic acid receptor and neuronal nitric oxide synthase, con-currently. Moreover, Bis（n）-Cognitin could inhibit β-amyloid-induced neurotoxicity, decrease glutamate-induced excitotoxici-ty, reduce oxidative stress, improve learning and memory, and protect against neuronal apoptosis in various in vitro and in vivo models, suggesting that bis （ n ）-Cognitin are potential anti-AD drug candidates.

关 键 词：阿尔采末病 他克林双联体 多靶点 神经保护 分子机制 乙酰胆碱酯酶 Β-淀粉样蛋白 

分 类 号：R-05[医药卫生] R745.702.2