CAJ | 학술논문

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,“一药多靶位冶药物可能是防治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。
아이채말병( Alzheimer's disease, AD)시다인소、다배절궤제개도적복잡질병,“일약다파위야약물가능시방치AD최유전도적방향。신형익뇌쌍련체[ Bis ( n )-Cognitin ]시본연구소조개조자타극림적고활성항AD쌍련체。실험연구표명,Bis( n)-Cognitin가동시작용을선담감지매、β-분비매、N-갑기-D-천동안산수체、신경원형일양화담합매등다개AD중요파표,구유억제β-정분양단백신경독성、조단신경흥강성독성、강저양화응격화선립체손상、개선동물학습기억능력、재체대항신경세포조망등작용,겁유가능성위미래방치AD적고효약물。
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.