A soluble activin type IIB receptor improves function in a mouse model of amyotrophic lateral sclerosis
A soluble activin type IIB receptor improves function in a mouse model of amyotrophic lateral sclerosis
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DOI：
10.1016/j.expneurol.2009.02.017
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发表时间：
2009-06-01
影响因子：
5.3
通讯作者：
Wagner, Kathryn R.
中科院分区：
文献类型：
--
作者：
Morrison, Brett M.;Lachey, Jennifer L.;Wagner, Kathryn R.
肌萎缩性侧索硬化症（ALS）是一种以进行性虚弱为特征的神经系统疾病，发病数年内因呼吸衰竭而死亡。肌生长抑制素是tgf - β超家族的一员，主要在肌肉中表达，并作为肌肉生长的负调节因子。在正常和疾病动物模型中，减弱肌肉生长抑制素已被证明可以产生增加的肌肉质量和力量。在本研究中，用可溶性激活素受体IIB型（ActRIIB.mFc）处理ALS小鼠模型（SOD1（G93A）转基因小鼠），该受体是除tgf - β超家族的其他配体外，公认的肌生长抑制素内源性信号受体。ActRIIB。无论是在症状出现前还是在症状出现后，mFc治疗都会延迟虚弱的发作，增加体重和握力，并增大肌肉尺寸。ActRIIB治疗。mFc不增加SOD1（G93A）转基因小鼠的存活率或神经肌肉连接处的神经支配。ActRIIB的药物治疗。在SOD1（G93A）转基因小鼠中，mFc在所有测量中都优于肌肉生长抑制素基因缺失。ActRIIB对SOD1（G93A）转基因小鼠功能的改善。mFc在开发tgf - β途径抑制剂以增加ALS患者肌肉力量方面是令人鼓舞的。(C) 2009爱思唯尔公司版权所有。
Amyotrophic lateral sclerosis (ALS) is a neurologic disease characterized by progressive weakness that results in death within a few years of onset by respiratory failure. Myostatin is a member of the TGF-beta superfamily that is predominantly expressed in muscle and acts as a negative regulator Of Muscle growth. Attenuating myostatin has previously been shown to produce increased muscle mass and strength in normal and disease animal models. In this study, a mouse model of ALS (SOD1(G93A) transgenic mice) was treated with a soluble activin receptor, type IIB (ActRIIB.mFc) which is a putative endogenous signaling receptor for myostatin in addition to other ligands of the TGF-beta superfamily. ActRIIB.mFc treatment produces a delay in the onset of weakness, an increase in body weight and grip strength, and an enlargement of muscle size whether initiated pre-symptomatically or after symptom onset. Treatment with ActRIIB.mFc did not increase survival or neuromuscular junction innervation in SOD1(G93A) transgenic mice. Pharmacologic treatment with ActRIIB.mFc was superior in all measurements to genetic deletion of myostatin in SOD1(G93A) transgenic mice. The improved function of SOD1(G93A) transgenic mice following treatment with ActRIIB.mFc is encouraging for the development of TGF-beta pathway inhibitors to increase muscle strength in patients with ALS. (C) 2009 Elsevier Inc. All rights reserved.