Considerable evidences suggest a link between autophagy dysfunction, protein aggregation, and neurodegenerative diseases. Given that autophagy is a conserved intracellular housekeeping process, modulation of autophagy flux in various model organisms have highlighted its importance for maintaining proteostasis. In postmitotic cells such as neurons, compromised autophagy is sufficient to cause accumulation of ubiquitinated aggregates, neuronal dysfunction, degeneration, and loss of motor coordination-all hallmarks of neurodegenerative diseases. Reciprocally, enhanced autophagy flux augments cellular and organismal health, in addition to extending life span. These genetic studies not-withstanding a plethora of small molecule modulators of autophagy flux have been reported that alleviate disease symptoms in models of neurodegenerative diseases. This review summarizes the potential of such molecules to be, perhaps, one of the first autophagy drugs for treating these currently incurable diseases.

中文翻译：

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调节神经退行性疾病中自噬的药理学工具。

大量证据表明自噬功能障碍，蛋白质聚集和神经退行性疾病之间存在联系。鉴于自噬是保守的细胞内管家过程，在各种模型生物中自噬通量的调节突出了其对维持蛋白稳定的重要性。在有丝分裂后的细胞（如神经元）中，自噬受损足以引起泛素化聚集物的积累，神经元功能障碍，变性和运动协调丧失，这是神经退行性疾病的所有标志。相反，增强的自噬通量除了延长寿命外，还可以增强细胞和机体的健康。这些遗传研究尽管有大量自噬通量的小分子调节剂，但已报道它们减轻了神经退行性疾病模型中的疾病症状。