ABSTRACT

Treatment of central nervous system (CNS) demyelination is greatly hindered by lack of the knowledge regarding to underlying molecular mechanisms as well as therapeutic agents. Here, we report a novel small molecule agent, gastrodin (GAS), which can significantly promote CNS myelination in in vivo mice models. By using high-throughput sequencing analysis, we discover a key long non-coding RNA Gm7237 that can enhance CNS myelination and is up-regulated by GAS. Through using bioinformatic analysis and experimental validations, we further unravel that microRNA-142a (miR-142a) and its target myelin gene regulatory factor (MRF) is under the direct regulation by Gm7237. Finally, we demonstrate that Gm7237/miR-142a/MRF axis is the key pathway involved in CNS myelination mediated by GAS. Overall, our results provide not only a novel agent for therapeutic treatment of CNS demyelination but also a molecular basis responsible for GAS-promoted CNS myelination.

 抽象的

由于缺乏有关潜在分子机制和治疗药物的知识，中枢神经系统（CNS）脱髓鞘的治疗受到极大阻碍。在这里，我们报道了一种新型小分子药物天麻素（GAS），它可以在体内小鼠模型中显着促进中枢神经系统髓鞘形成。通过高通量测序分析，我们发现了一个关键的长链非编码RNA Gm7237，它可以增强中枢神经系统髓鞘形成，并被GAS上调。通过生物信息学分析和实验验证，我们进一步揭示了microRNA-142a（miR-142a）及其靶髓磷脂基因调节因子（MRF）受到Gm7237的直接调节。最后，我们证明 Gm7237/miR-142a/MRF 轴是 GAS 介导的中枢神经系统髓鞘形成的关键途径。总的来说，我们的结果不仅提供了一种治疗中枢神经系统脱髓鞘的新药，而且还为 GAS 促进的中枢神经系统髓鞘形成提供了分子基础。