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.
出处
《中国药理学通报》
CAS
CSCD
北大核心
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)