Levine Beth, Packer Milton, Codogno Patrice
J Clin Invest. 2015 Jan;125(1):14-24. doi: 10.1172/JCI73938. Epub 2015 Jan 2.
Defects in autophagy have been linked to a wide range of medical illnesses, including cancer as well as infectious, neurodegenerative, inflammatory, and metabolic diseases. These observations have led to the hypothesis that autophagy inducers may prevent or treat certain clinical conditions. Lifestyle and nutritional factors, such as exercise and caloric restriction, may exert their known health benefits through the autophagy pathway. Several currently available FDA-approved drugs have been shown to enhance autophagy, and this autophagy-enhancing action may be repurposed for use in novel clinical indications. The development of new drugs that are designed to be more selective inducers of autophagy function in target organs is expected to maximize clinical benefits while minimizing toxicity. This Review summarizes the rationale and current approaches for developing autophagy inducers in medicine, the factors to be considered in defining disease targets for such therapy, and the potential benefits of such treatment for human health.
自噬缺陷与多种医学疾病相关,包括癌症以及感染性、神经退行性、炎症性和代谢性疾病。这些观察结果引发了一种假说,即自噬诱导剂可能预防或治疗某些临床病症。生活方式和营养因素,如运动和热量限制,可能通过自噬途径发挥其已知的健康益处。目前几种已获美国食品药品监督管理局(FDA)批准的药物已被证明可增强自噬,这种自噬增强作用可能被重新用于新的临床适应症。预计开发出在靶器官中更具选择性的自噬功能诱导剂的新药,将在使毒性最小化的同时最大化临床益处。本综述总结了在医学中开发自噬诱导剂的基本原理和当前方法、确定此类治疗的疾病靶点时需考虑的因素,以及这种治疗对人类健康的潜在益处。