Key Laboratory of Brain Science, Zunyi Medical University, Zunyi, China.
Guizhou Key Laboratory of Anesthesia and Organ Protection, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
RNA Biol. 2021 Sep;18(9):1279-1290. doi: 10.1080/15476286.2020.1841976. Epub 2020 Nov 5.
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 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.
中枢神经系统(CNS)脱髓鞘的治疗受到缺乏对潜在分子机制以及治疗药物的了解的极大阻碍。在这里,我们报告了一种新型小分子药物,天麻素(GAS),它可以显著促进小鼠模型中的 CNS 髓鞘形成。通过高通量测序分析,我们发现了一种关键的长非编码 RNA Gm7237,它可以增强 CNS 髓鞘形成,并被 GAS 上调。通过使用生物信息学分析和实验验证,我们进一步揭示了 microRNA-142a(miR-142a)及其靶基因髓鞘基因调节因子(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 CNS 髓鞘形成所涉及的关键途径。总之,我们的结果不仅为 CNS 脱髓鞘的治疗提供了一种新的药物,也为 GAS 促进 CNS 髓鞘形成的分子基础提供了依据。