神经炎症抑制剂用于阿尔茨海默症的药物研发简

阿尔茨海默症（Alzheimer’s disease，AD）的致病机制尚不明确，至今仍然缺乏有效的治疗药物，并且临床研究中的候选药物也多以失败告终. 因此，对于AD这样一种复杂的疾病，单纯依赖分子靶标的现代药物研发策略难以奏效，迫切需要结合以细胞和动物药效为重心的经典药物研发策略，方有望打破AD新药开发的瓶颈. 鉴于神经元的退化和凋亡始终是AD发生、发展的中心环节，因此通过抑制大脑小胶质细胞的过度活化，进而抑制神经炎症的发展可以阻止AD的恶化进程. 本文综述了如何通过神经免疫细胞的表型筛选，确立神经炎症抑制剂，进而辅以AD动物模型的体内药效评价，获得能够显著提高模型动物的记忆和认知能力的活性分子，并结合本课题组最新的研究进展，对本领域进行了初步的讨论和展望.

The development of anti-neuroinflammatory agents for the treatment of Alzheimer’s disease

Since Alzheimer's disease (AD) is complicated with unclear mechanisms, multiple strategies might be needed to explore anti-AD therapies. Over-activated microglia-mediated neuroinflammation is suggested as the primary contributor of memory impairment and cognitive decline of AD patients. Anti-neuroinflammatory agents identified through conventional drug discovery paradigm including microglia-based cell screenings and AD mouse model verification may be able to combat the devastating disease. This paper highlights the development of anti-neuroinflammatory agents that have shown promise in vitro and/or in vivo by attenuating microglial activation and/or cognitive decline. These agents support the concept and represent important chemical probes for the development of anti-neuroinflammatory drugs for the treatment of AD.