Gastrodin promotes CNS myelination via a lncRNA Gm7237/miR-142a/MRF pathway

天麻素通过 lncRNA Gm7237/miR-142a/MRF 通路促进中枢神经系统髓鞘形成

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作者:Yue Shu, Tianyuan Luo, Mingda Wang, Yu Zhang, Lin Zhang, Zhi Xiao, Qianxing Wang, Qiang Zhang, Jia Zou, Changyin Yu, Shangfu Xu, Tian Yu, Liang Zhou, Shouyang Yu

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.

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