Myostatin inhibition slows muscle atrophy in rodent models of amyotrophic lateral sclerosis
Myostatin inhibition slows muscle atrophy in rodent models of amyotrophic lateral sclerosis
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DOI：
10.1016/j.nbd.2006.05.009
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发表时间：
2006-09-01
影响因子：
6.1
通讯作者：
Walsh, Frank S.
中科院分区：
文献类型：
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作者：
Holzbaur, Erika L. F.;Howland, David S.;Walsh, Frank S.
肌萎缩侧索硬化症（Amyotrophic lateral sclerosis，ALS）是一种导致运动神经元细胞死亡的神经退行性疾病，近年来的研究表明，非神经元细胞参与了ALS的病理机制。肌生长抑制素是肌肉生长的负调节剂，其功能可以使用中和抗体抑制。在这项研究中，我们使用转基因小鼠和大鼠ALS模型来测试抗肌生长抑制素抗体治疗是否减缓肌肉萎缩，运动神经元丢失或疾病发作和进展。在疾病发作之前和疾病早期期间，在肌生长抑制素抗体处理的SOD1（G93A）小鼠和大鼠中观察到肌肉质量和强度的显著增加。到疾病晚期，与未治疗的对照组相比，治疗组动物中仅膈肌保持显著差异。肌生长抑制素抑制剂既不延迟疾病发作，也不延长SOD1（G93A）小鼠或大鼠的生存期。总之，这些结果表明，肌肉生长抑制素的抑制不能防止运动神经元退行性疾病的发作和进展。然而，在早期疾病期间骨骼肌的保存和通过晚期疾病维持的改善的膈肌形态和功能表明，抗肌肉生长抑制素治疗可以促进ALS中肌肉功能的一些改善。(c)2006年爱思唯尔公司All rights reserved.
Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease leading to motor neuron cell death, but recent studies suggest that non-neuronal cells may contribute to the pathological mechanisms involved. Myostatin is a negative regulator of muscle growth whose function can be inhibited using neutralizing antibodies. In this study, we used transgenic mouse and rat models of ALS to test whether treatment with anti-myostatin antibody slows muscle atrophy, motor neuron loss, or disease onset and progression. Significant increases in muscle mass and strength were observed in myostatin-antibody-treated SOD1(G93A) mice and rats prior to disease onset and during early-stage disease. By late stage disease, only diaphragm muscle remained significantly different in treated animals in comparison to untreated controls. Myostatin inhibition did not delay disease onset nor extend survival in either the SOD1(G93A) mouse or rat. Together, these results indicate that inhibition of myostatin does not protect against the onset and progression of motor neuron degenerative disease. However, the preservation of skeletal muscle during early-stage disease and improved diaphragm morphology and function maintained through late stage disease suggest that anti-myostatin therapy may promote some improved muscle function in ALS. (c) 2006 Elsevier Inc. All rights reserved.