microRNAs in CNS Disorders
microRNAs in CNS Disorders
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DOI：
10.1007/s12017-009-8066-1
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发表时间：
2009-09-01
影响因子：
3.5
通讯作者：
Wahlestedt, Claes
中科院分区：
文献类型：
--
作者：
Kocerha, Jannet;Kauppinen, Sakari;Wahlestedt, Claes
近年来，随着广泛的测序工作对人类基因组和转录组的概况产生了新的见解，转录和翻译调控的传统范式发生了转变。哺乳动物中枢神经系统 (CNS) 中已鉴定出数百种称为 microRNA (miRNA) 的非编码调节 RNA 分子，据报道它们在神经元功能的许多方面发挥着关键作用。基于 miRNA 的转录后调控的破坏与一系列中枢神经系统疾病有关，因为预计一种 miRNA 会影响众多下游 mRNA 靶标的表达。由 miRNA 介导的复杂分子网络形成了一种强大的机制，可以在人脑发育过程中对细胞事件做出快速而有效的反应。最近的研究已经确定了一部分 miRNA 在阿尔茨海默病和精神分裂症中的分子和最终致病作用，包括其下游 CNS mRNA 靶标的特征，例如 β 分泌酶 (BACE1) 和钙调蛋白依赖性蛋白激酶 II (CaMKII)。在这里，我们概述了与 CNS 疾病相关的 miRNA 研究的当前进展，并强调了 LNA（锁核酸）修饰的寡核苷酸在检测和调节 miRNA 活性中的效用。
In recent years, there has been a shift in the conventional paradigms for transcriptional and translational regulation as extensive sequencing efforts have yielded new insights into the landscape of the human genome and transcriptome. Hundreds of non-coding regulatory RNA molecules called microRNAs (miRNAs) have been identified in the mammalian central nervous system (CNS) and are reported to mediate pivotal roles in many aspects of neuronal functions. Disruption of miRNA-based post-transcriptional regulation has been implicated in a range of CNS disorders as one miRNA is predicted to impact the expression of numerous downstream mRNA targets. The intricate molecular networks mediated by an miRNA form a robust mechanism for rapid and potent responses to cellular events throughout the development of the human brain. Recent studies have identified a molecular and ultimately pathogenic role for a subset of miRNAs in Alzheimer's disease and schizophrenia, including the characterization of their downstream CNS mRNA targets, such as beta-secretase (BACE1) and calmodulin-dependent protein kinase II (CaMKII). Here, we present an overview of the current progress in miRNA research related to CNS disorders and also highlight the utility of LNA (locked nucleic acid)-modified oligonucleotides in the detection and modulation of miRNA activity.