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复杂miRNA网络在中枢和外周损伤及轴突再生中的功能整合

Functional integration of complex miRNA networks in central and peripheral lesion and axonal regeneration.

作者信息

Ghibaudi M, Boido M, Vercelli A

机构信息

Department of Neuroscience "Rita Levi Montalcini", Neuroscience Institute Cavalieri Ottolenghi, University of Torino, Italian Institute of Neuroscience, Italy.

Department of Neuroscience "Rita Levi Montalcini", Neuroscience Institute Cavalieri Ottolenghi, University of Torino, Italian Institute of Neuroscience, Italy.

出版信息

Prog Neurobiol. 2017 Nov;158:69-93. doi: 10.1016/j.pneurobio.2017.07.005. Epub 2017 Aug 3.

Abstract

New players are emerging in the game of peripheral and central nervous system injury since their physiopathological mechanisms remain partially elusive. These mechanisms are characterized by several molecules whose activation and/or modification following a trauma is often controlled at transcriptional level. In this scenario, microRNAs (miRNAs/miRs) have been identified as main actors in coordinating important molecular pathways in nerve or spinal cord injury (SCI). miRNAs are small non-coding RNAs whose functionality at network level is now emerging as a new level of complexity. Indeed they can act as an organized network to provide a precise control of several biological processes. Here we describe the functional synergy of some miRNAs in case of SCI and peripheral damage. In particular we show how several small RNAs can cooperate in influencing simultaneously the molecular pathways orchestrating axon regeneration, inflammation, apoptosis and remyelination. We report about the networks for which miRNA-target bindings have been experimentally demonstrated or inferred based on target prediction data: in both cases, the connection between one miRNA and its downstream pathway is derived from a validated observation or is predicted from the literature. Hence, we discuss the importance of miRNAs in some pathological processes focusing on their functional structure as participating in a cooperative and/or convergence network.

摘要

在外周和中枢神经系统损伤的研究领域中,新的参与者不断涌现,因为它们的生理病理机制仍部分不为人知。这些机制的特征在于多种分子,创伤后这些分子的激活和/或修饰通常在转录水平受到调控。在这种情况下,微小RNA(miRNA/miR)已被确定为协调神经或脊髓损伤(SCI)中重要分子途径的主要参与者。miRNA是小型非编码RNA,其在网络水平的功能正逐渐呈现出一种新的复杂程度。实际上,它们可以作为一个有组织的网络,对多种生物学过程进行精确控制。在此,我们描述了在脊髓损伤和外周损伤情况下一些miRNA的功能协同作用。特别是,我们展示了几种小RNA如何协同作用,同时影响协调轴突再生、炎症、凋亡和髓鞘再生的分子途径。我们报告了基于实验证明或根据靶标预测数据推断出miRNA-靶标结合的网络:在这两种情况下,一种miRNA与其下游途径之间的联系均源自经过验证的观察结果或从文献中预测得出。因此,我们讨论了miRNA在某些病理过程中的重要性,重点关注它们作为参与合作和/或汇聚网络的功能结构。

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