Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Exp Neurol. 2011 Jun;229(2):214-25. doi: 10.1016/j.expneurol.2011.01.017. Epub 2011 Feb 2.
Spinal muscular atrophy (SMA) is a devastating genetic motoneuron disease leading to infant death. No effective therapy is currently available. It has been suggested that β-lactam antibiotics such as ceftriaxone may offer neuroprotection in motoneuron diseases. Here, we investigate the therapeutic effect of ceftriaxone in a murine model of SMA. Treated animals present a modest, but significant ameliorated neuromuscular phenotype and increased survival, which correlate with protection of neuromuscular units. Whole gene expression profiling in treated mice demonstrates modifications in several genes including those involved in RNA metabolism toward wild-type. The neuroprotective effect seems to be mediated by multiple mechanisms that encompass the increase of the glutamate transporter Glt1, the transcription factor Nrf2, as well as SMN protein. This study provides the first evidence of a potential positive effect of this class of molecules in SMA. Further investigation of analogs with increased and more specific therapeutic effects warrants the development of useful therapies for SMA.
脊髓性肌萎缩症（SMA）是一种破坏性的遗传性运动神经元疾病，可导致婴儿死亡。目前尚无有效的治疗方法。有人提出，β-内酰胺类抗生素如头孢曲松可能对运动神经元疾病有神经保护作用。在这里，我们研究了头孢曲松在 SMA 小鼠模型中的治疗效果。治疗组动物表现出轻微但显著改善的神经肌肉表型和存活率提高，这与运动神经元单位的保护相关。在治疗组小鼠中进行的全基因表达谱分析表明，包括涉及 RNA 代谢的基因在内的多个基因发生了修饰，使其向野生型靠拢。神经保护作用似乎是通过多种机制介导的，其中包括增加谷氨酸转运体 Glt1、转录因子 Nrf2 以及 SMN 蛋白的表达。这项研究首次提供了此类分子在 SMA 中具有潜在积极作用的证据。进一步研究具有更高和更特异性治疗效果的类似物，有望为 SMA 开发出有用的治疗方法。
