MicroRNA and epilepsy: profiling, functions and potential clinical applications.

MicroRNA and epilepsy: profiling, functions and potential clinical applications.
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DOI:
10.1097/wco.0000000000000079
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发表时间:
2014-04
影响因子:
4.8
通讯作者:
Henshall DC
Henshall DC
中科院分区:
医学2区
文献类型:
--
作者:
Henshall DC

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综述最近研究实验性和人类癫痫的microRNA变化的研究概况,并概述这一研究领域的临床应用的机制、治疗和诊断潜力。在实验性和人类癫痫的一系列研究中,已经对microRNAs进行了大规模的表达谱分析,microRNAs是细胞中控制蛋白质水平的关键调节分子。超过100种不同的microRNAs的水平在海马体中被发现增加或减少,其中超过20种在不止一项研究中被发现,包括更高水平的miR-23a、miR-34a、miR-132和miR-146a。在癫痫的脑组织中也发现了参与microRNA生物发生和功能的酶的水平改变,包括迪格尔和阿加乔特2。使用基于寡核苷酸的抑制剂的功能研究支持microRNAs在控制细胞死亡、突触结构、炎症和免疫反应中的作用。最后,数据显示,引发癫痫的脑损伤在生物液中产生独特的microRNA图谱。MicroRNA是癫痫中控制蛋白质水平的一个潜在的重要机制。因此,microRNAs可能被用于预防或干扰癫痫,以及作为癫痫发生的诊断生物标志物。
To provide a synthesis of recent profiling studies investigating microRNA changes in experimental and human epilepsy and outline mechanistic, therapeutic and diagnostic potentials of this research area for clinical practice. A series of studies in experimental and human epilepsy have undertaken large-scale expression profiling of microRNAs, key regulatory molecules in cells controlling protein levels. Levels of over 100 different microRNAs were found to either increase or decrease in the hippocampus, of which more than 20 were identified in more than one study, including higher levels of miR-23a, miR-34a, miR-132 and miR-146a. Altered levels of enzymes involved in microRNA biogenesis and function, including Dicer and Argonaute 2, have also been found in epileptic brain tissue. Functional studies using oligonucleotide-based inhibitors support roles for microRNAs in the control of cell death, synaptic structure, inflammation and the immune response. Finally, data show brain injuries that precipitate epilepsy generate unique microRNA profiles in biofluids. MicroRNA represents a potentially important mechanism controlling protein levels in epilepsy. As such, microRNAs might be targeted to prevent or disrupt epilepsy as well as serve as diagnostic biomarkers of epileptogenesis.