促进β-淀粉样肽聚集为目标的阿尔茨海默病治疗新策略探讨

Treatment of Alzheimer’s disease by promoting the aggregation of smallβ-amyloid peptides

阿尔茨海默病(Alzheimer’s disease,AD)是一种具有复杂病理学特征的老年失智症.淀粉样蛋白级联假说与寡聚体毒性假说在解释AD病理机制方面占据主导地位.AD患者数量庞大,但目前尚未发现治疗AD的有效疗法,多数药物在Ⅲ期临床试验的结果不够理想.本文对影响β-淀粉样肽(β-amyloid,Aβ)聚集的国内外相关研究进展进行总结,并阐述小分子化合物加速Aβ纤维形成过程的可能机理.这一过程与传统疗法相悖却在动物模型中取得了相当好的疗效,意味着促进Aβ聚集可能成为AD治疗的新策略,为新药开发指明了新方向.

Alzheimer’s disease(AD)is a type of senile dementia with complex pathological features.The amyloid cascade and oligomer toxicity hypotheses play a dominant role in explaining the pathological mechanism of AD.A large number of patients develop AD,but no effective treatment is available,and most drugs have not had good results in phase Ⅲ clinical trials.In this study,research progress on the aggregation of β-amyloid(Aβ)is summarized,and the possible mechanism of small molecule compounds accelerating the formation of Aβ fibers is described.This process contrasts with traditional therapy but has achieved quite good efficacy in animal models,suggesting that promoting Aβ aggregation may be a new strategy for treating AD and indicating a new direction for drug development.