Cava Claudia, Manna Ida, Gambardella Antonio, Bertoli Gloria, Castiglioni Isabella
Institute of Molecular Bioimaging and Physiology (IBFM), National Research Council (CNR), Milan, Italy.
Institute of Molecular Bioimaging and Physiology (IBFM), National Research Council (CNR), Section of Germaneto, 88100 Catanzaro, Italy.
Mol Ther Nucleic Acids. 2018 Dec 7;13:275-290. doi: 10.1016/j.omtn.2018.09.008. Epub 2018 Sep 13.
Epilepsy includes a group of disorders of the brain characterized by an enduring predisposition to generate epileptic seizures. Although familial epilepsy has a genetic component and heritability, the etiology of the majority of non-familial epilepsies has no known associated genetic mutations. In epilepsy, recent epigenetic profiles have highlighted a possible role of microRNAs in its pathophysiology. In particular, molecular profiling identifies a significant number of microRNAs (miRNAs) altered in epileptic hippocampus of both animal models and human tissues. In this review, analyzing molecular profiles of different animal models of epilepsy, we identified a group of 20 miRNAs commonly altered in different epilepsy-animal models. As emerging evidences highlighted the poor overlap between signatures of animal model tissues and human samples, we focused our analysis on miRNAs, circulating in human biofluids, with a principal role in epilepsy hallmarks, and we identified a group of 8 diagnostic circulating miRNAs. We discussed the functional role of these 8 miRNAs in the epilepsy hallmarks. A few of them have also been proposed as therapeutic molecules for epilepsy treatment, revealing a great potential for miRNAs as theranostic molecules in epilepsy.
癫痫包括一组脑部疾病，其特征是具有产生癫痫发作的持久倾向。虽然家族性癫痫有遗传成分和遗传性，但大多数非家族性癫痫的病因尚无已知相关基因突变。在癫痫中，最近的表观遗传学特征突出了微小RNA在其病理生理学中的可能作用。特别是，分子分析确定了在动物模型和人体组织的癫痫海马体中大量改变的微小RNA（miRNA）。在本综述中，通过分析不同癫痫动物模型的分子特征，我们鉴定出一组在不同癫痫动物模型中普遍改变的20种miRNA。由于新出现的证据强调了动物模型组织和人类样本特征之间的重叠性较差，我们将分析重点放在了在人体生物流体中循环的、在癫痫特征中起主要作用的miRNA上，并鉴定出一组8种具有诊断价值的循环miRNA。我们讨论了这8种miRNA在癫痫特征中的功能作用。其中一些还被提议作为癫痫治疗的治疗分子，揭示了miRNA作为癫痫诊疗分子的巨大潜力。
