Chao Xiaojuan, Ding Wen-Xing
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, United States.
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, United States.
Adv Pharmacol. 2019;85:109-131. doi: 10.1016/bs.apha.2019.01.008. Epub 2019 Feb 24.
Alcoholic liver disease (ALD) is one of the major causes of chronic liver disease worldwide. Currently, no successful treatments are available for ALD. The pathogenesis of ALD is characterized as simple steatosis, fibrosis, cirrhosis, alcoholic hepatitis (AH), and eventually hepatocellular carcinoma (HCC). Autophagy is a highly conserved intracellular catabolic process, which aims at recycling cellular components and removing damaged organelles in response to starvation and stresses. Therefore, autophagy is considered as an important cellular adaptive and survival mechanism under various pathophysiological conditions. Recent studies from our lab and others suggest that chronic alcohol consumption may impair autophagy and contribute to the pathogenesis of ALD. In this chapter, we summarize recent progress on the role and mechanisms of autophagy in the development of ALD. Understanding the roles of autophagy in ALD may offer novel therapeutic avenues against ALD by targeting these pathways.
酒精性肝病(ALD)是全球慢性肝病的主要病因之一。目前,尚无针对ALD的成功治疗方法。ALD的发病机制表现为单纯性脂肪变性、纤维化、肝硬化、酒精性肝炎(AH),最终发展为肝细胞癌(HCC)。自噬是一种高度保守的细胞内分解代谢过程,旨在回收细胞成分并清除受损细胞器,以应对饥饿和应激。因此,自噬被认为是各种病理生理条件下重要的细胞适应性和生存机制。我们实验室及其他机构最近的研究表明,长期饮酒可能损害自噬并促进ALD的发病机制。在本章中,我们总结了自噬在ALD发展中的作用和机制的最新进展。了解自噬在ALD中的作用可能通过靶向这些途径为对抗ALD提供新的治疗途径。