Most neurodegenerative diseases show a disruption of autophagic function and display abnormal accumulation of toxic protein aggregates that promotes cellular stress and death. Therefore, induction of autophagy has been proposed as a reasonable strategy to help neurons clear abnormal protein aggregates and survive. The kinase mammalian target of rapamycin (mTOR) is a major regulator of the autophagic process and is regulated by starvation, growth factors, and cellular stressors. The phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) pathway, which promotes cellular survival, is the main modulator upstream of mTOR, and alterations in this pathway are common in neurodegenerative diseases, e.g. Alzheimer’s disease (AD) and Parkinson’s disease (PD). In the present work we revised mammalian target of rapamycin complex 1 (mTORC1) pathway and mTORC2 as a complementary an important element in mTORC1 signaling. In addition, we revised the extracellular signal regulated kinase (ERK) pathway, which has become relevant in the regulation of the autophagic process and cellular survival through mTORC2 signaling. Finally, we summarize novel compounds that promote autophagy and neuronal protection in the last five years.

大多数神经退行性疾病表现出自噬功能的破坏，并显示有毒蛋白质聚集体的异常积累，从而促进细胞应激和死亡。因此，已经提出诱导自噬是一种合理的策略，可以帮助神经元清除异常的蛋白质聚集体并存活。雷帕霉素的哺乳动物激酶靶标（mTOR）是自噬过程的主要调节剂，受饥饿，生长因子和细胞应激因子的调节。磷酸肌醇3-激酶（PI3K）/蛋白激酶B（Akt）途径可促进细胞存活，是mTOR上游的主要调节剂，该途径的改变在神经退行性疾病中很常见，例如阿尔茨海默氏病（AD）和帕金森氏病（PD）。在本工作中，我们修订了雷帕霉素复合物1（mTORC1）途径和mTORC2的哺乳动物靶标，作为mTORC1信号传导中的重要补充元素。此外，我们修订了细胞外信号调节激酶（ERK）途径，该途径已通过mTORC2信号调节自噬过程和细胞存活。最后，我们总结了最近五年中促进自噬和神经元保护的新型化合物。