Role of FoxO proteins in the regulation of skeletal muscle anabolism, catabolism and insulin sensitivity

肌肉组织丢失或肌肉萎缩是许多常见健康问题的标志，包括糖尿病、癌症、库欣综合征、败血症、艾滋病和肾衰竭。在过去的2-3年里，在了解哺乳动物骨骼肌分解代谢(肌肉萎缩)和合成代谢(肌肉生长)的分子调控方面取得了重要进展。众所周知，某些转录因子家族，即FoxO蛋白，能够激活分解代谢途径。然而，最近，我们发现FoxO蛋白也通过阻断合成代谢途径导致肌肉萎缩。我们的新数据强调了靶向FoxO蛋白的重要性，FoxO蛋白是治疗发生肌肉组织萎缩的人类疾病的药物。这项提案将研究阻止FoxO蛋白作用的方法，希望能防止肌肉萎缩。

Loss of muscle tissue or muscle wasting is a hallmark of many common health problems including diabetes, cancer, Cushing's syndrome, sepsis, HIV-Aids and renal failure. In the past 2-3 years important progress has been made in understanding the molecular regulation of both catabolism (muscle wasting) and anabolism (muscle growth) within mammalian skeletal muscles. It has been known for some time that a certain family of transcription factors, known as FoxO proteins, activate catabolic pathways. However, recently, we have shown that FoxO proteins also cause muscle wasting by blocking anabolic pathways. Our new data heighten the importance of targeting FoxO proteins are therapeutics for human diseases where muscle tissue wasting occurs. This proposal will investigate methods that will allow for blocking the action of FoxO proteins in the hope that muscle wasting can be prevented.