阿尔茨海默病中靶向β-淀粉样蛋白药物的研究进展  

Research progress of drugs targeting amyloid-β protein in Alzheimer's disease

作　　者：郭小岚 孙悦 时政 GUO Xiao-lan;SUN Yue;SHI Zheng(Sichuan Industrial Institute of Antibiotics ＆ School of Medicine, Chengdu University, Chengdu 610106, China)

机构地区：[1]成都大学四川抗菌素工业研究所&医学院,成都610106

出　　处：《中国新药杂志》2018年第12期1364-1371,共8页Chinese Journal of New Drugs

基　　金：四川省青年科技基金杰出青年基金项目(2017JQ0060);四川省科技厅科技支撑计划(2016NZ0060)

摘　　要：阿尔茨海默病(Alzheimer's disease,AD)是一种常见于老年人的神经退行性疾病。其主要的病理学特征为β-淀粉样蛋白(β-amyloid protein,Aβ)聚集形成老年斑(senile plaque,SP)以及细胞内的Tau蛋白过度磷酸化导致形成的神经纤维缠结(neuro fibrillary tangle,NFT)和神经元的丢失。现存的发病机制假说主要有:神经元兴奋性毒性假说、Aβ毒性假说、Tau蛋白假说等,其中Aβ毒性假说占主导地位。目前,AD的治疗药物基本上都是依据上述假说而展开的,已进入临床使用的治疗药物大多都是通过调节乙酰胆碱从而发挥作用,但是均只能减缓其发病进程,还不能逆转疾病进程。现处于研究阶段靶向Aβ的治疗药物中又主要分为以aducanumab为代表的免疫治疗药物和以elenbecestat为代表的小分子治疗药物。根据Aβ毒性蛋白的发病机制,我们拟从2个方面阐明靶向Aβ从而治疗AD。本文以Aβ为靶点对现阶段临床研究药物进行分析研究,以期为AD靶向药物的研发提供新的方向。Alzheimer’s disease（ AD） is one of the common neurogenerative diseases in old people. The main clinical pathologic features are that amyloid-β（ Aβ） aggregates into senile plaque（ SP）,and the hyperphosphorylated Tau protein accumulates to form neuro fibrillary tangles（ NFT） and neuro loss. Currently,neural excitotoxicity hypothesis,Aβ hypothesis and Tau protein hypothesis are the most popular pathogenesis hypotheses of AD,among these hypotheses Aβ toxicity is the dominant. At present,most medicines for AD are basically based on the above hypotheses. Most clinical medicines regulate acetylcholine system but can only slow down the progression of AD instead of reversing the disease process. Among the drugs targeting Aβ,the main representations are aducanumab,which represents immunotherapy drugs,and elenbecestat,which is a small molecule inhibitor. According to AD pathogeneses,we reviewed research progress of the drugs targeting Aβ protein from two aspects. This article takes Aβ as a target to analyze and research the clinical research drugs,in order to provide a new direction for the development of targeted drugs for AD.

关 键 词：阿尔茨海默病 Β-淀粉样蛋白 靶向药物 临床研究 研究进展 

分 类 号：R961[医药卫生—药理学]