Equipe 11 labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers, 75006, Paris, France.
Cell Biology and Metabolomics Platforms, Gustave Roussy Cancer Campus, 94805, Villejuif, France.
Cell Death Differ. 2019 Mar;26(4):680-689. doi: 10.1038/s41418-019-0290-0. Epub 2019 Feb 6.
The relentless efforts of thousands of researchers have allowed deciphering the molecular machinery that regulates and executes autophagy, thus identifying multiple molecular targets to enhance or block the process, rendering autophagy "druggable". Autophagy inhibition may be useful for preserving the life of cells that otherwise would succumb to excessive self-digestion. Moreover, autophagy blockade may reduce the fitness of cancer cells or interrupt metabolic circuitries required for their growth. Autophagy stimulation is probably useful for the prevention or treatment of aging, cancer (when stimulation of immunosurveillance is the therapeutic goal), cardiovascular disease, cystic fibrosis, infection by intracellular pathogens, obesity, and intoxication by heavy metals, just to mention a few examples. Epidemiological evidence suggests broad health-improving effects for lifestyles, micronutrients, and drugs that favor autophagy. In this review, we discuss the role of autophagy in disease pathogenesis while focusing on the question, which disease will become the first clinically approved indication for therapeutic autophagy modulation.
数千名研究人员的不懈努力使得人们能够破译调节和执行自噬的分子机制，从而确定了多个分子靶点来增强或阻断该过程，使自噬成为“可药物化”的。自噬抑制可能有助于保护那些否则会因过度自我消化而死亡的细胞的生命。此外，自噬阻断可能会降低癌细胞的适应性或中断其生长所需的代谢途径。自噬刺激可能有助于预防或治疗衰老、癌症（当刺激免疫监视是治疗目标时）、心血管疾病、囊性纤维化、细胞内病原体感染、肥胖和重金属中毒等疾病，仅举几例。流行病学证据表明，有利于自噬的生活方式、微量营养素和药物具有广泛的改善健康的作用。在这篇综述中，我们讨论了自噬在疾病发病机制中的作用，同时重点讨论了哪个疾病将成为第一个经临床批准的治疗性自噬调节适应症。
