SMN-targeted therapeutics for spinal muscular atrophy: are we SMArt enough yet?
SMN-targeted therapeutics for spinal muscular atrophy: are we SMArt enough yet?
复制标题
SMN 靶向治疗脊髓性肌萎缩症：我们的 SMArt 足够了吗？
DOI：
10.1172/jci74142
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Swoboda,KathrynJ
中科院分区：
文献类型：
--
作者：
Swoboda,KathrynJ
脊髓性肌萎缩症(SMA)是最常见、最致命的常染色体隐性遗传病之一。运动神经元存活基因1(SMN1)的纯合缺失和导致的SMN蛋白缺陷主要表现为运动神经元变性；然而，大量的新数据支持SMN缺陷在疾病发病机制中的更广泛影响。在这一期的JCI中，Kariya及其同事使用一系列表达SMN的转基因小鼠展示了SMN耗竭对远端运动单位的相对选择性影响，在这些转基因小鼠中，结构性SMN基因敲除遵循正常发育的不同时期。他们的观察为小鼠对SMN的时间需求提供了进一步的见解，重新推测了何时何地补充SMN对于SMA患者的最佳结果是必要的。
Spinal muscular atrophy (SMA) remains one of the most common and lethal autosomal recessive diseases. Homozygous deletion of survival of motor neuron 1 (SMN1) and resulting SMN protein deficiency manifests predominantly with motor neuron degeneration; however, a wealth of emerging data supports a broader influence of SMN deficiency in disease pathogenesis. In this issue of theJCI, Kariya and colleagues demonstrate the relatively selective impact of SMN depletion on the distal motor unit using a series ofSMN2-expressing transgenic mice in which constitutive SMN knockdown follows variable periods of normal development. Their observations provide further insights regarding the temporal requirements for SMN in mice, renewing speculation about when and where repletion of SMN is necessary for optimal outcomes in SMA patients.