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当前研究哺乳动物轴突再生的表观遗传学研究的进展与局限性。

Advances and Limitations of Current Epigenetic Studies Investigating Mammalian Axonal Regeneration.

机构信息

Laboratory for Neuroregeneration, Centre for Restorative Neuroscience, Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.

出版信息

Neurotherapeutics. 2018 Jul;15(3):529-540. doi: 10.1007/s13311-018-0636-1.

Abstract

Axonal regeneration relies on the expression of regenerative associated genes within a coordinated transcriptional programme, which is finely tuned as a result of the activation of several regenerative signalling pathways. In mammals, this chain of events occurs in neurons following peripheral axonal injury, however it fails upon axonal injury in the central nervous system, such as in the spinal cord and the brain. Accumulating evidence has been suggesting that epigenetic control is a key factor to initiate and sustain the regenerative transcriptional response and that it might contribute to regenerative success versus failure. This review will discuss experimental evidence so far showing a role for epigenetic regulation in models of peripheral and central nervous system axonal injury. It will also propose future directions to fill key knowledge gaps and to test whether epigenetic control might indeed discriminate between regenerative success and failure.

摘要

轴突再生依赖于再生相关基因在协调的转录程序中的表达,这是由于几个再生信号通路的激活而精细调节的。在哺乳动物中,这种事件链发生在周围轴突损伤后的神经元中,但在中枢神经系统(如脊髓和大脑)的轴突损伤中却失败了。越来越多的证据表明,表观遗传控制是启动和维持再生转录反应的关键因素,它可能有助于再生的成功与失败。这篇综述将讨论迄今为止的实验证据,表明表观遗传调控在外周和中枢神经系统轴突损伤模型中的作用。它还将提出未来的方向,以填补关键的知识空白,并测试表观遗传控制是否确实可以区分再生的成功与失败。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab2b/6095777/d803267b4400/13311_2018_636_Fig1_HTML.jpg

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