Nat Med：microRNA-134基因可引发癫痫症

近日，刊登在国际著名杂志Nature Medicine上的一篇研究报告中，来自爱尔兰皇家外科医师学会的研究者发现了一个和癫痫症有关的新基因，这就为潜在治疗癫痫疾病提供了新的药物靶点。

研究者重点研究了一种名为microRNA的一类基因，这类基因控制细胞内部蛋白质的合成。研究者研究了microRNA-134，并且发现microRNA-134在大脑中水平较高的话容易引发癫痫患者病人疾病发作。研究者使用药物类似小分子antagomir来“锁住”microRNA-134，然后将其从大脑中移除，可以组织癫痫发作。

研究者David说，我们一直在寻找，到底是大脑哪里出问题了从而引发癫痫的发作，我们的研究发现了新的和癫痫相关的基因，并且我们也揭示了如何以新发现基因为靶点来使用药物，从而降低大脑发作的敏感性，进而降低发病频率。而且结果显示，antagomir药物可以保护大脑细胞免受长期癫痫发作的影响。

在爱尔兰癫痫影响着37，000人的健康，三个癫痫病人中有两个人长期进行着药物治疗，这项研究可以为癫痫病人的治疗提供新的思路。

相关研究由爱尔兰科学基金提供资助。

编译自：New Epilepsy Gene Identified; Possible New Treatment Option

doi:10.1038/nm.2834
PMC:
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Silencing microRNA-134 produces neuroprotective and prolonged seizure-suppressive effects

Eva M Jimenez-Mateos,1 Tobias Engel,1 Paula Merino-Serrais,2 Ross C McKiernan,1 Katsuhiro Tanaka,1 Genshin Mouri,1 Takanori Sano,1 Colm O'Tuathaigh,3 John L Waddington,3 Suzanne Prenter,3 Norman Delanty,4 Michael A Farrell,5 Donncha F O'Brien,6 Ronán M Conroy,7 Raymond L Stallings,3, 8 Javier DeFelipe2 & David C Henshall1

Temporal lobe epilepsy is a common, chronic neurological disorder characterized by recurrent spontaneous seizures. MicroRNAs (miRNAs) are small, noncoding RNAs that regulate post-transcriptional expression of protein-coding mRNAs, which may have key roles in the pathogenesis of neurological disorders. In experimental models of prolonged, injurious seizures (status epilepticus) and in human epilepsy, we found upregulation of miR-134, a brain-specific, activity-regulated miRNA that has been implicated in the control of dendritic spine morphology. Silencing of miR-134 expression in vivo using antagomirs reduced hippocampal CA3 pyramidal neuron dendrite spine density by 21% and rendered mice refractory to seizures and hippocampal injury caused by status epilepticus. Depletion of miR-134 after status epilepticus in mice reduced the later occurrence of spontaneous seizures by over 90% and mitigated the attendant pathological features of temporal lobe epilepsy. Thus, silencing miR-134 exerts prolonged seizure-suppressant and neuroprotective actions; determining whether these are anticonvulsant effects or are truly antiepileptogenic effects requires additional experimentation.