Systemic treatment with a novel basic fibroblast growth factor mimic small-molecule compound boosts functional recovery after spinal cord injury
Systemic treatment with a novel basic fibroblast growth factor mimic small-molecule compound boosts functional recovery after spinal cord injury
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DOI：
10.1371/journal.pone.0236050
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发表时间：
2020-07-17
期刊：
影响因子：
3.7
通讯作者：
Ishiguro, Naoki
中科院分区：
文献类型：
--
作者：
Imagama, Shiro;Ogino, Ryoko;Ishiguro, Naoki
神经营养因子被认为具有很好的神经保护和再生潜力，从而促进运动功能的有益作用。它们可能在各种神经疾病的细胞/组织移植中发挥重要作用。然而，这些营养因子对中枢神经系统（CNS）的临床应用由于其独特的生物活性特性而引起了有问题的副作用。在开发反映碱性成纤维细胞生长因子（bFGF）的有益特性的合成化合物的过程中，我们进行了筛选刺激以触发FGF受体的细胞内酪氨酸磷酸化并导致神经元中的后续细胞内信号传导的候选物。小的合成分子SUN 13837的特征在于模拟bFGF的有益特性，这被称为其应用于CNS时的特异性活性。更值得注意的是，SUN 13837消除了诱导非神经元体细胞增殖的生物活性。在药理学、行为学、生理学和组织学研究的基础上，本研究报告SUN 13837是一种有前途的治疗大鼠脊髓破坏性损伤的合成化合物。
Neurotrophic factors have been regarded having promising potentials for neuronal protection and regeneration, and thus promoting beneficial effects of kinesiological functions. They can be suspected to play important roles in cell/tissue grafting for various neural diseases. The clinical applications of such trophic factors to the central nervous system (CNS), however, have caused problematic side effects on account of the distinctive bioactive properties. In the course of developing synthetic compounds reflecting beneficial properties of basic fibroblast growth factor (bFGF), we conducted screening candidates that stimulate to trigger the intracellular tyrosine phosphorylation of FGF receptor and lead to the subsequent intracellular signaling in neurons. A small synthetic molecule SUN13837 was characterized by mimicking the beneficial properties of bFGF, which have been known as its specific activities when applied to CNS. What is more remarkable is that SUN13837 is eliminated the bioactivity to induce cell proliferation of non-neuronal somatic cells. On the bases of studies of pharmacology, behavior, physiology and histology, the present study reports that SUN13837 is characterized as a promising synthetic compound for treatment of devastating damages onto the rat spinal cord.