以淀粉样蛋白为靶点的抗阿尔茨海默病药物研发进展

Review on the development of anti-alzheimer's drugs targeting amyloid peptide

阿尔茨海默病(AD)是以认知功能障碍、精神行为异常和日常生活能力减退为特征的神经退行性疾病,目前已成为威胁老年人健康的"第四大杀手"。AD的典型病理特征为神经元外淀粉样蛋白(Aβ)沉积、神经元内神经原纤维缠结(NFT)和神经元丢失。尽管AD的具体发病机制目前尚不明确,但很多动物实验研究结果均提示,Aβ沉积是引发AD的最主要因素,因此很多研究者均致力于以Aβ为靶点的抗AD药物研发。本文综述了以Aβ为靶点的单克隆抗体药物和小分子药物的具体作用机制和临床研发进展,为抗AD药物的进一步研发奠定基础。

Alzheimer ＇s disease(AD） is a neurodegenerative disease characterized by cognitive deficit,behavioral disturbance and decline of daily life activity. It is the 4 th cause of death in the elderly. The typical pathological features of AD are deposition of neuronal extracellular amyloid(Aβ）,appearance of neuronal neurofibrillary tangles(NFT）and neuronal loss. Although the pathogenesis of AD is still unclear,many animal studies have suggested that Aβ deposition is the most important factor in AD. Thus Aβ peptide is regarded as a promising target for the development of novel anti-AD drugs. This paper reviews the mechanism of action and clinical development of monoclonal antibodies and small molecule drugs targeting Aβ peptide and provides a basis for further development of anti-AD drugs.