自噬启动因子ULK1的生物学功能与靶向治疗研究进展

Research progress in biological function and targeted therapeutic application of the autophagic initiator ULK1

UNC-51样激酶1(ULK1)作为一种丝氨酸/苏氨酸激酶是哺乳动物中的自噬启动因子,也是酵母中Atg1的同源蛋白.近年来,大量研究揭示了ULK1的结构特征及其生物学功能,并阐明了其调控自噬的途径及其与多种疾病的关系.最新研究还发现了一系列直接或间接靶向ULK1调节自噬的小分子化合物,为开发靶向自噬的新候选药物提供了线索.该文综述了ULK1作为自噬启动因子的复杂生物学功能、与多种疾病的关系及其潜在的靶向治疗应用.

UNC-51-like kinase 1(ULK1),the yeast Atg1 ortholog,is well-known to be the serine/threonine kinase and the autophagic initiator in mammals.Recently,extensive studies have illustrated the partial structure characteristics and the biological function of ULK1,as well as its regulatory autophagic pathways and relationships with diverse diseases.More interestingly,some small-molecule compounds have been reported to directly or indirectly target ULK1-modulating autophagy,thereby providing some clues on exploiting novel candidate drugs that target autophagy.In this review,we discuss the complicated biological function of ULK1 and its associations with human diseases,as well as its potential targeted therapeutic applications.