阿尔茨海默病药物研发最新进展  

Advances in drug development for Alzheimer’s disease

作　　者：穆峣 赵慧敏 刘昊晨 柳晓泉[1] MU Yao;ZHAO Huimin;LIU Haochen;LIU Xiaoquan(Center of Drug Metabolism and Pharmacokinetics,China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]中国药科大学代谢动力学研究中心,南京211198

出　　处：《中国药科大学学报》2024年第6期816-825,共10页Journal of China Pharmaceutical University

基　　金：国家自然科学基金项目(No.81903703)。

摘　　要：阿尔茨海默病(Alzheimer's disease,AD)是一种涉及到多种病理过程的神经退行性疾病,临床主要表现为记忆缺失和认知功能障碍。AD的病理过程复杂,发病机制尚不清楚,目前存在多种假说如β-淀粉样蛋白(β-amyloid,Aβ)沉积、Tau蛋白过度磷酸化、神经炎症和神经元突触丢失等,研究人员以此为基础开展药物研发。2021年之前,美国食品药品监督管理局批准的药物均以调节神经递质为靶点,然而疗效非常有限。近几年来,两款抗Aβ单抗药物的获批给患者带来了一定的临床获益,但仍没能完全满足临床需求,AD药物研发仍亟待探索新的机制和靶点。目前针对AD的新机制和新靶标药物研发主要聚焦以下几个方向:抗Aβ药物、抗Tau蛋白药物、抗神经炎症免疫药物、改善线粒体功能药物、促进神经发生药物以及突触保护类药物。本文对这几个方向近10年来进入临床试验的AD新药进行概述,详细介绍了部分代表药物,并结合本课题组研究内容给出总结与展望。Alzheimer’s disease(AD)is a neurodegenerative disorder involving multiple pathological processes,clinically characterized by memory loss and cognitive impairment.The pathological processes of AD are complex,and the etiology remains unclear.Currently,there are various hypotheses includingβ-amyloid(Aβ)deposition,tau protein hyperphosphorylation,neuroinflammation,and synaptic loss,upon which researchers base their drug development efforts.Prior to 2021,drugs approved by the U.S.Food and Drug Administration(FDA)had targeted neurotransmitter modulation,but their efficacy was limited.In recent years,the approval of two anti-Aβmonoclonal antibody drugs has brought some clinical benefits to patients,yet they have not fully met clinical needs,which had highlighted the urgent necessity for exploration of new mechanisms and targets in AD drug development.Presently,research on novel mechanisms and targets for AD drug development focuses primarily on several directions:anti-Aβdrugs,anti-Tau protein drugs,anti-neuroinflammation immunotherapies,mitochondrial function-improving drugs,neurogenesis-promoting drugs,and synapse-protective drugs.This paper provides an overview of AD drugs entering clinical trials in the past decade in these directions,details some representative drugs,and concludes with prospects,integrating findings from our research group.

关 键 词：阿尔茨海默病 药物研发 临床试验 抗Aβ药物 抗Tau蛋白药物 抗神经炎症免疫药物 

分 类 号：R965[医药卫生—药理学]