Barberi Laura, Dobrowolny Gabriella, Pelosi Laura, Giacinti Cristina, Musarò Antonio
Department of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy.
Endocr Dev. 2009;14:29-37. doi: 10.1159/000207474. Epub 2009 Feb 27.
In the last decade, dramatic progress has been made in elucidating the molecular defects underlying a number of muscle diseases. With the characterization of mutations responsible for muscle dysfunction in several inherited pathologies, and the identification of novel signaling pathways, subtle alterations in which can lead to significant defects in muscle metabolism, the field is poised to devise successful strategies for treatment of this debilitating and often fatal group of human ailments. Yet progress has been slow in therapeutic applications of our newly gained knowledge. The complexity of muscle types, the intimate relationship between structural integrity and mechanical function, and the sensitivity of skeletal muscle to metabolic perturbations have impeded rapid progress in successful clinical intervention. The relatively poor regenerative properties of striated muscle compound the devastating effects of muscle degeneration. Perhaps the most difficult hurdle is the sheer volume of tissue that must be treated to effect a significant improvement in quality of life. Recent studies on the role of insulin-like growth factor-1 in skeletal muscle growth and homeostasis have excited new interest in this important mediator of anabolic pathways and suggest promising new avenues for intervention in catabolic disease. In this review, we will discuss the potential therapeutic role of local insulin-like growth factor 1 in the treatment of muscle wasting associated with muscle diseases.
在过去十年中，在阐明多种肌肉疾病背后的分子缺陷方面取得了显著进展。随着在几种遗传性疾病中对导致肌肉功能障碍的突变进行了特征描述，并确定了新的信号通路，这些信号通路的细微改变可导致肌肉代谢出现重大缺陷，该领域已准备好制定成功的策略来治疗这一使人衰弱且往往致命的人类疾病群体。然而，将我们新获得的知识应用于治疗方面的进展一直很缓慢。肌肉类型的复杂性、结构完整性与机械功能之间的密切关系以及骨骼肌对代谢扰动的敏感性，阻碍了成功临床干预的快速进展。横纹肌相对较差的再生特性加剧了肌肉退化的破坏性影响。也许最困难的障碍是为显著改善生活质量而必须治疗的组织量巨大。最近关于胰岛素样生长因子 -1 在骨骼肌生长和体内平衡中的作用的研究，激发了人们对这一合成代谢途径重要介质的新兴趣，并为干预分解代谢疾病提出了有希望的新途径。在这篇综述中，我们将讨论局部胰岛素样生长因子 1 在治疗与肌肉疾病相关的肌肉萎缩中的潜在治疗作用。
