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微小 RNA 与癫痫发生中的靶基因。

MicroRNAs and target genes in epileptogenesis.

机构信息

Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.

Department of Pediatrics, First Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

Epilepsia. 2020 Oct;61(10):2086-2096. doi: 10.1111/epi.16687. Epub 2020 Sep 18.

DOI:10.1111/epi.16687
PMID:32944964
Abstract

Epilepsy is a chronic brain dysfunction. Current antiepileptic medicines cannot prevent epileptogenesis. Increasing data have shown that microRNAs (miRNAs) are selectively altered within the epileptic hippocampi of experimental models and human tissues, and these alterations affect the genes that control epileptogenesis. Furthermore, manipulation of miRNAs in animal models can modify epileptogenesis. As a result, miRNAs have been proposed as promising targets for treating epilepsy. We searched PubMed using the terms "microRNAs/miRNAs AND epilepsy", "microRNAs/miRNAs AND epileptogenesis", and "microRNAs/miRNAs AND seizure". We selected the articles in which the relationship between miRNAs and target gene(s) was validated and manipulation of miRNAs in in vivo epilepsy models modified epileptogenesis during the chronic phase via gene regulation. A total of 13 miRNAs were found in the present review. Based on the current analysis of miRNAs and their target gene(s), each miRNA has limitations as a potential epilepsy target. Importantly, miR-211 or miR-128 transgenic mice displayed seizures. These findings highlight new developments for epileptogenesis prevention. Developing novel strategies to modify epileptogenesis will be effective in curing epilepsy patients. This article provides an overview of the clinical application of miRNAs as novel targets for epilepsy.

摘要

癫痫是一种慢性脑功能障碍。目前的抗癫痫药物不能预防癫痫发生。越来越多的数据表明,微小 RNA(miRNA)在实验模型和人类组织的癫痫海马体中选择性改变,这些改变影响控制癫痫发生的基因。此外,在动物模型中对 miRNA 的操作可以改变癫痫发生。因此,miRNA 已被提议作为治疗癫痫的有希望的靶点。我们使用术语“microRNAs/miRNAs AND epilepsy”、“microRNAs/miRNAs AND epileptogenesis”和“microRNAs/miRNAs AND seizure”在 PubMed 上进行了搜索。我们选择了那些验证了 miRNA 与靶基因之间关系的文章,以及在体内癫痫模型中操纵 miRNA 通过基因调控在慢性期改变癫痫发生的文章。本综述共发现了 13 种 miRNA。基于 miRNA 及其靶基因的当前分析,每种 miRNA 作为潜在的癫痫靶点都有其局限性。重要的是,miR-211 或 miR-128 转基因小鼠出现癫痫发作。这些发现强调了预防癫痫发生的新进展。开发修饰癫痫发生的新策略将对治疗癫痫患者有效。本文概述了 miRNA 作为癫痫新靶点的临床应用。

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