Institut Necker-Enfants Malades (INEM), INSERM U1151-CNRS UMR 8253, F-75993 Paris, France; email:
Université Paris Descartes-Sorbonne Paris Cité, F-75012 Paris, France.
Annu Rev Pharmacol Toxicol. 2017 Jan 6;57:375-398. doi: 10.1146/annurev-pharmtox-010716-104936.
Macroautophagy (hereafter called autophagy) is a vacuolar, lysosomal pathway for catabolism of intracellular material that is conserved among eukaryotic cells. Autophagy plays a crucial role in tissue homeostasis, adaptation to stress situations, immune responses, and the regulation of the inflammatory response. Blockade or uncontrolled activation of autophagy is associated with cancer, diabetes, obesity, cardiovascular disease, neurodegenerative disease, autoimmune disease, infection, and chronic inflammatory disease. During the past decade, researchers have made major progress in understanding the three levels of regulation of autophagy in mammalian cells: signaling, autophagosome formation, and autophagosome maturation and lysosomal degradation. As we discuss in this review, each of these levels is potentially druggable, and, depending on the indication, may be able to stimulate or inhibit autophagy. We also summarize the different modulators of autophagy and their potential and limitations in the treatment of life-threatening diseases.
自噬（下文称为自噬）是真核细胞中一种溶酶体途径的液泡性、溶酶体性细胞内物质分解代谢过程，在组织稳态、应激情况适应、免疫反应和炎症反应调节中发挥着关键作用。自噬的阻断或不受控制的激活与癌症、糖尿病、肥胖症、心血管疾病、神经退行性疾病、自身免疫性疾病、感染和慢性炎症性疾病有关。在过去的十年中，研究人员在理解哺乳动物细胞中自噬的三个调节水平方面取得了重大进展：信号转导、自噬体形成以及自噬体成熟和溶酶体降解。正如我们在这篇综述中讨论的那样，这些水平中的每一个都具有潜在的可药物修饰性，并且根据适应证，可以刺激或抑制自噬。我们还总结了不同的自噬调节剂及其在治疗危及生命的疾病中的潜力和局限性。
