Faculty of Biology, Technion Institute of Technology, Haifa, 32000, Israel.
Cambridge Institute for Medical Research, Department of Medicine, University of Cambridge, Cambridge, CB2 0XY, UK.
Nat Rev Drug Discov. 2015 Jan;14(1):58-74. doi: 10.1038/nrd4467.
Atrophy occurs in specific muscles with inactivity (for example, during plaster cast immobilization) or denervation (for example, in patients with spinal cord injuries). Muscle wasting occurs systemically in older people (a condition known as sarcopenia); as a physiological response to fasting or malnutrition; and in many diseases, including chronic obstructive pulmonary disorder, cancer-associated cachexia, diabetes, renal failure, cardiac failure, Cushing syndrome, sepsis, burns and trauma. The rapid loss of muscle mass and strength primarily results from excessive protein breakdown, which is often accompanied by reduced protein synthesis. This loss of muscle function can lead to reduced quality of life, increased morbidity and mortality. Exercise is the only accepted approach to prevent or slow atrophy. However, several promising therapeutic agents are in development, and major advances in our understanding of the cellular mechanisms that regulate the protein balance in muscle include the identification of several cytokines, particularly myostatin, and a common transcriptional programme that promotes muscle wasting. Here, we discuss these new insights and the rationally designed therapies that are emerging to combat muscle wasting.
肌肉萎缩可发生在因不活动（例如，在石膏固定时）或失神经支配（例如，脊髓损伤患者）而导致特定肌肉萎缩的情况下。老年人（一种称为肌肉减少症的疾病）会出现全身性肌肉消耗；在禁食或营养不良时会出现这种情况；并且在许多疾病中也会出现这种情况，包括慢性阻塞性肺疾病、癌症相关恶病质、糖尿病、肾衰竭、心力衰竭、库欣综合征、败血症、烧伤和创伤。肌肉质量和力量的迅速丧失主要是由于蛋白质分解过度，通常伴随着蛋白质合成减少。这种肌肉功能的丧失会导致生活质量下降、发病率和死亡率增加。运动是预防或减缓萎缩的唯一公认方法。但是，正在开发几种有前途的治疗药物，并且我们对调节肌肉中蛋白质平衡的细胞机制的理解取得了重大进展，其中包括确定了几种细胞因子，特别是肌肉生长抑制素，以及促进肌肉消耗的常见转录程序。在这里，我们讨论了这些新的见解以及正在出现的合理设计的治疗方法，以对抗肌肉消耗。
