基于小胶质细胞功能障碍的阿尔茨海默病药物研发

Drug discovery for Alzheimer's disease based on the functional disturbance of microglia

阿尔茨海默病(Alzheimer’s disease,AD)俗称老年痴呆,是严重威胁全球中老年人健康的神经退行性疾病。由于发病机制尚不明确,发病进程不可逆转,造成了AD难防难治。AD的主要症状是记忆、认知力的降低,源于神经元受损,但是基于神经元的AD新药研发近年来频遭失败,急需探索新的治疗路径。小胶质细胞作为中枢神经系统的最重要的免疫细胞,对神经元和大脑的功能维护起着重要的作用,小胶质细胞的过度活化导致的神经炎症反应也是AD的重要病理特征,参与到AD发病的各个环节,因此抑制小胶质细胞的过度活化,抑制神经炎症有望阻止AD的恶化进程。本文主要通过小胶质细胞与神经元之间的相互关联来论述靶向神经胶质细胞治疗AD的可能性,并分析了小分子药物的研究现状和神经炎症抑制剂用于AD治疗的重要意义。

Alzheimer＇s disease（AD）is the most prevalent neurodegenerative disease of the brain.Due to the uncertain pathogenesis,prevention and treatment of AD is difficult.Clinic symptoms of AD including progressive loss of memory and spatial orientation are rooted in synaptic and neuronal loss.Unsuccessful clinical trials of several candidate drugs based on amyloid hypothesis and tau hypothesis have led to exploration of new approaches.Neuro-inflammation characterized by dysfunction in microglia is believed to be the hallmark of AD and also the initiator of downstream responses in neurodegeneration.Alleviate microglia activation and neuro-inflammation may delay AD development.In this paper,we describe the current literature on interaction between microglia and neuron,and review the progress in AD drug discovery and neu ro-inflammatory inhibitors for treatment of AD.