miR-23a靶向调控ADAM10基因在颞叶癫痫中的作用及其机制研究

项目名称： miR-23a靶向调控ADAM10基因在颞叶癫痫中的作用及其机制研究

项目编号： No.81673413

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 医药、卫生

项目作者： 朱新建

作者单位： 东南大学

项目金额： 25万元

中文摘要： 微小RNA(microRNA，miRNA)是一类内源性非编码单链RNA分子，新近的研究发现miRNA在颞叶癫痫发生、发展过程中具有重要作用。申请者在预实验中发现miR-23a在颞叶癫痫模型小鼠海马组织中被显著上调，并通过生物信息学方法预测到miR-23a的靶基因ADAM10，且证实了miR-23a与ADAM10的靶向关系。本项目在前期研究的基础上，提出miR-23a→ADAM10通路调控癫痫发生并在癫痫发生后调控海马结构病理性损伤，影响海马神经环路兴奋性的新假说。如果该假说得到证实，将有望通过选择性干预miR-23a→ADAM10信号通路遏制癫痫发生，并在癫痫发生后减轻海马结构病理性损伤，达到有效控制癫痫疾病的目的。本项目拟通过药理学、分子生物学等手段，结合细胞与动物模型，在细胞和分子水平阐明miR-23a在颞叶癫痫疾病中的作用和调控机制，为探寻癫痫药物靶标提供前瞻性思路。

中文关键词： miR-23a；ADAM10；颞叶癫痫；海马；癫痫发生

英文摘要： Micro RNA (miRNA) is a group endogenous non-coding single strand RNA which is recognized to be involved in the development of epilepsy. Our preliminary data showed that miR-23a was up-regulated in the hippocampus of TLE animal models. Furthermore, we predicted and validated miR-23a target gene ADAM10. Based on our previous study, this project proposed a hypothesis that miR-23a-ADAM10 pathway regulates epileptogenesis and epilepsy-associated hippocampal pathological changes, which affect the excitability of hippocampal circuit. If this hypothesis is proved, we could suppress epileptogenesis and alleviate hippocampal injury by selectively interfering miR-23a-ADAM10 pathway and therefore prevent and cure epilepsy. In this project, we sought to determine the biological effect of miR-23a in TLE and to reveal the molecular mechanisms of how miR-23a regulation of epileptogenesis by using the methods of pharmacology and molecular biology in vitro and in vivo. We believe this study would give the perspective in seeking new therapeutic strategy and developing new anti-epileptic drugs.

英文关键词： miR-23a;ADAM10;temporal lobe epilepsy;hippocampus;epileptogenesis