新型体外胆碱酯酶抑制剂筛选体系的构建

目的:构建新型简便可靠的体外胆碱酯酶抑制剂筛选体系。方法:从SD大鼠大脑和血清中提取乙酰胆碱酯酶(AChE)和丁酰胆碱酯酶(BuChE),应用Ellman比色法构建体外AChE和BuChE抑制剂筛选实验体系。结果:选择10倍稀释的雄性大鼠脑匀浆液〔蛋白浓度(1.69±0.10)mg·mL^(-1)〕和5倍稀释的血清作为AChE/BuChE酶源,使用AChE/BuChE抑制剂他克林作为参考。他克林对AChE/BuChE的半数抑制浓度(IC50)分别为262 nmol·L^(-1)和168 nmol·L^(-1),体外胆碱酯酶抑制剂筛选体系构建成功。在等量蛋白浓度情况下,雌性大鼠脑匀浆液中AChE酶活性为雄性大鼠的1.84倍。结论:本研究从大鼠大脑和血清里分别提取AChE和BuChE粗酶,构建了一种新型的简单易行且稳定可靠的AChE/BuChE抑制剂筛选平台。

Novel anti-AD dimeric leads:from relieving symptoms to modifying diseases via multi-targets

Alzheimer disease(AD) has now become the most common brain disorder among the older population. In addition, the currently existing therapeutics only offer temporary symptomatic relieves. Therefore, further research and development of more efficacious and disease-modifying agents for the prevention, treatment and restoration of AD will have tremendous value from both scientific, and economic standpoints. Over the past few years, our series of studies have identified several highly promising anti-AD dimeric leads, with disease-modifying potentials. In this presentation, the latest progress on the neuroprotective and disease modifying effects and the underlying mechanisms of those candidates will be comprehensively illustrated and discussed.

中西药杂合体多靶点抗阿尔茨海默病研究进展

阿尔茨海默病(Alzheimer's disease,AD)是最为常见的中枢神经系统退行性疾病。目前临床AD治疗药物包括多奈哌齐(donepezil)、利斯的明(rivastigmine)、美金刚(memantine),以及源于天然药用植物石蒜科雪花莲的加兰他敏(galantamine)和千层塔的石杉碱甲(huperzine A)。但这些药物大多作用于单一靶点,无法延缓AD进程。原因在于:随着AD病程进展,各种AD神经毒素相互影响,神经元损伤级联性放大。