McFarlane Craig, Sharma Mridula, Kambadur Ravi
Nanyang Technological University, School of Biological Sciences, Genomics and Genetics Division, Singapore.
Curr Opin Clin Nutr Metab Care. 2008 Jul;11(4):422-7. doi: 10.1097/MCO.0b013e32830007e2.
To describe the most relevant recent observations concerning the molecular mechanisms behind myostatin-induced muscle wasting.
The main theme of this review is to summarize the biology and function of myostatin. Myostatin is a secreted growth factor that negatively regulates muscle growth. While inactivation of myostatin leads to muscle growth in vivo, excess levels of myostatin induces cachectic-like muscle wasting. Molecular analyses reveal that excess levels of myostatin induce Atrogin-1 expression by reducing Akt phosphorylation and thereby increasing FoxO1 activity. Recent findings have further speculated that myostatin may also play a role in cardiac cachexia.
As myostatin is a potent inducer of muscle wasting, antagonists to myostatin have been speculated to have great therapeutic value in alleviating muscle wasting. Indeed, myostatin peptide antagonists and antibodies have shown great promise in containing muscle loss in animal models of muscle wasting. Given the beneficial effects of myostatin antagonists in animal models, clinical trials are underway with myostatin antibodies, peptibodies and soluble receptor. Therefore, this review article on the role of myostatin in muscle wasting is highly relevant to current themes in muscle biology.
描述近期关于肌肉生长抑制素诱导肌肉萎缩背后分子机制的最相关观察结果。
本综述的主题是总结肌肉生长抑制素的生物学特性和功能。肌肉生长抑制素是一种分泌型生长因子，对肌肉生长起负向调节作用。虽然肌肉生长抑制素失活在体内会导致肌肉生长，但过量的肌肉生长抑制素会诱导恶病质样肌肉萎缩。分子分析表明，过量的肌肉生长抑制素通过降低Akt磷酸化从而增加FoxO1活性来诱导Atrogin-1表达。近期研究进一步推测，肌肉生长抑制素可能在心脏恶病质中也起作用。
由于肌肉生长抑制素是肌肉萎缩的强效诱导剂，因此推测肌肉生长抑制素拮抗剂在减轻肌肉萎缩方面具有巨大的治疗价值。事实上，肌肉生长抑制素肽拮抗剂和抗体在肌肉萎缩动物模型中已显示出在控制肌肉损失方面的巨大前景。鉴于肌肉生长抑制素拮抗剂在动物模型中的有益作用，目前正在进行肌肉生长抑制素抗体、肽抗体和可溶性受体的临床试验。因此，这篇关于肌肉生长抑制素在肌肉萎缩中作用的综述文章与当前肌肉生物学主题高度相关。
