自噬在阿尔茨海默病中的作用机制及治疗前景

The role of autophagy in Alzheimer's disease and its potential for therapy

自噬作为细胞内一种清除非必需或异常物质的基本代谢途径,在阿尔茨海默病的发病过程中扮演重要角色。自噬过程中可产生β-淀粉样蛋白,同时自噬溶酶体系统也直接参与Aβ和tau蛋白清除机制。溶酶体功能障碍和自噬囊泡大量聚集导致Aβ和tau蛋白聚集,可能是阿尔茨海默病的病因之一。基于此,恢复受损的自噬溶酶体功能在阿尔茨海默病治疗中具有重要潜在价值。本文就自噬途径如何介导阿尔茨海默病的发病及其药物治疗前景作一概述。

Autophagy, the basic intracellular mechanism for catabolic and continuous clearance of unnecessary or dysfunctional components, occupies a crucial role in Alzheimer＇s disease （AD）. Multiple studies both in vitro and in vivo have demonstrated that amyloid-β protein （Aβ） can be generated during autophagy, while lysosomal system is also directly implicated in the elimination of Aβ and tau protein. Pathophysically, both in AD models and AD patients, lysosomal dysfunction and autophagic vacuoles accumulation provide direct and objective evidence of impaired dynamic process of autophagy, which leads to the aggregation of Aβ and tau and thus contributes to the pathogenesis of AD. Accumulating studies in vivo have shown promising therapies targeting autophagic process, as activating autophagy may be beneficial to the early stages of AD and restoring lysosomal proteolysis may be favorable for the late stages of AD. This review mainly discusses the mechanism of autophagy-induced AD and the promising autophagy-related treatments for AD.