自噬与Nrf2信号通路之间联系的研究进展

Advances in the Relationship between Autophagy and Nrf2 Pathway

自噬是人体内常见且重要的生理现象之一,对于维持细胞的稳定及代谢需要具有关键意义。核因子E2相关因子(nuclear factor erythroid-derived factor 2-related factor,Nrf2)是调控细胞对抗外来异物和氧化损伤的关键转录因子,Nrf2信号通路在抗肿瘤、抗应激等方面发挥着广泛的细胞保护功能。随着研究进展,发现自噬与Nrf2信号通路间存在着广泛的相互作用机制。抑制自噬会导致p62积累,进而结合Keap1(Kelch-like ECH-associated protein 1)而激活Nrf2信号通路;同时也有研究发现,磷脂酰肌醇-3-激酶/蛋白激酶B(phosphatidyl inositol 3-kinase/protein kinase B,PI3K/Akt)等自噬和Nrf2的共同调节通路、活性氧(reactive oxidative species,ROS)等因素也参与自噬与Nrf2之间的相互调控。该文将以近期关于Nrf2信号通路与自噬之间关系研究进展作一综述,希望为临床疾病治疗提供新的视角。

Autophagy is a common phenomenon in human body, which plays a vital role in maintaining cellular homeostasis and metabolism. Nuclear factor erythroid-derived factor 2-related factor （Nrf2） functions as a crucial transcriptional factor in terms of regulating the cellular response against foreign bodies and oxidative damages. With further researches, a wide range of the crosstalk between Nrf2 pathway and autophagy was disclosed. Previous researches have found that inhibiting autophagy leads to accumulation of p62, thus combined with Kelch-like ECH-associated protein 1 （Keapl） and activating Nrf2 pathway. In addition, phosphatidyl inositol 3-kinase/protein kinase B （PI3K/Akt） pathway, reactive oxidative species （ROS） and other factors also participate in regulation between autophagy and Nrf2. In this review, we will discuss the progress that has been made in dissecting the intersection of these two pathways, providing new perspectives for the clinical therapy.