Barcelona Hepatic Hemodynamic Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) - Hospital Clínic de Barcelona - CIBEREHD , Barcelona , Spain +34932275400 ext: 4306 ; +34932279856 ;
Expert Opin Investig Drugs. 2014 Jul;23(7):965-77. doi: 10.1517/13543784.2014.912274. Epub 2014 Apr 21.
Autophagy is a cellular process essential for survival and homeostasis that confers cellular protection toward a wide range of deleterious stimuli. It has a highly complex regulation with several autophagic proteins also belonging to other main signaling pathways as cell proliferation or apoptosis. In addition, autophagy has an important role in cell metabolism. Interest in the study of this process is rapidly rising and, in the past few years, autophagy has been implicated in a variety of hepatic diseases.
The review covers the research and investigational use of pharmacological strategies that modify autophagy in the treatment of liver diseases. Autophagy modulation in steatosis, steatohepatitis, viral hepatitis, fibrogenesis, cirrhosis, hepatocellular carcinoma and ischemia/reperfusion injury will be described, critically analyzed and discussed. Papers included in the present manuscript were selected from the PubMed search: liver + (macro)autophagy + each of the pathologies described above.
The complexity of autophagy creates significant controversy on the potential of its pharmacological modulation. A major requirement for drugs regulating autophagy in the treatment of liver diseases is that these should be liver-specific; moreover, they should primarily target one specific hepatic cell type.
自噬是一种对生存和体内平衡至关重要的细胞过程，它能为多种有害刺激提供细胞保护。自噬的调控非常复杂，一些自噬蛋白也属于细胞增殖或凋亡等其他主要信号通路。此外，自噬在细胞代谢中也起着重要作用。人们对这一过程的研究兴趣正在迅速上升，在过去的几年中，自噬已被牵涉到多种肝脏疾病中。
本综述涵盖了研究和调查性使用药理学策略来调节自噬治疗肝脏疾病的研究。将描述、批判性分析和讨论自噬在脂肪变性、脂肪性肝炎、病毒性肝炎、肝纤维化、肝硬化、肝细胞癌和缺血/再灌注损伤中的调节作用。本文献中包含的论文是从 PubMed 搜索中选择的：肝脏+（大）自噬+上述每一种病理。
自噬的复杂性对其药理学调节的潜力产生了重大争议。调节自噬治疗肝脏疾病的药物的一个主要要求是这些药物应该是肝脏特异性的；此外，它们应该主要针对一种特定的肝细胞类型。
