A selective Sema3A inhibitor enhances regenerative responses and functional recovery of the injured spinal cord
A selective Sema3A inhibitor enhances regenerative responses and functional recovery of the injured spinal cord
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DOI：
10.1038/nm1505
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发表时间：
2006-12-01
期刊：
影响因子：
82.9
通讯作者：
Okano, Hideyuki
中科院分区：
文献类型：
--
作者：
Kaneko, Shinjiro;Iwanami, Akio;Okano, Hideyuki
成年哺乳动物中枢神经系统（CNS）中的轴突在损伤后几乎不表现出再生。已经表明，几种轴突生长抑制剂阻止CNS轴突再生。最近的研究表明，semaphorin 3A（Sema 3A）是轴突再生的主要抑制剂之一。我们确定了一个强大的和选择性的抑制剂Sema 3A，SM-216289，从发酵液的真菌菌株。为了检查SM-216289在体内的作用，我们横切成年大鼠的脊髓，并将SM-216289施用到病变部位4周。用SM-216289处理的大鼠显示出损伤轴突的再生和/或保存显著增强，损伤部位的强大的Schwann细胞介导的髓鞘形成和轴突再生，凋亡细胞数量明显减少，血管生成显著增强，导致功能恢复明显改善。因此，Sema 3A对于脊髓损伤（SCI）后轴突再生和其他再生反应的抑制是必不可少的。这些结果支持使用Sema 3A抑制剂治疗人类SCI的可能性。
Axons in the adult mammalian central nervous system (CNS) exhibit little regeneration after injury. It has been suggested that several axonal growth inhibitors prevent CNS axonal regeneration. Recent research has demonstrated that semaphorin3A (Sema3A) is one of the major inhibitors of axonal regeneration. We identified a strong and selective inhibitor of Sema3A, SM-216289, from the fermentation broth of a fungal strain. To examine the effect of SM-216289 in vivo, we transected the spinal cord of adult rats and administered SM-216289 into the lesion site for 4 weeks. Rats treated with SM-216289 showed substantially enhanced regeneration and/or preservation of injured axons, robust Schwann cell-mediated myelination and axonal regeneration in the lesion site, appreciable decreases in apoptotic cell number and marked enhancement of angiogenesis, resulting in considerably better functional recovery. Thus, Sema3A is essential for the inhibition of axonal regeneration and other regenerative responses after spinal cord injury (SCI). These results support the possibility of using Sema3A inhibitors in the treatment of human SCI.