中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (1): 64-65.doi: 10.4103/1673-5374.175044

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

发育转录因子在年龄相关中枢神经系统疾病中的重新表达

  

  • 收稿日期:2015-11-03 出版日期:2016-01-15 发布日期:2016-01-15

Developmental transcription factors in age-related CNS disease: a phoenix rising from the ashes?

Robert B. White*, Meghan G. Thomas   

  1. School of Anatomy, Physiology & Human Biology, The University of Western Australia, Crawley, WA, Australia (White RB)
    Parkinson’s Centre, School of Medical Sciences, Edith Cowan University, Joondalup, WA, Australia (White RB, Thomas MG)
    Experimental and Regenerative Neuroscience, School of Animal Biology, The University of Western Australia, Crawley, WA, Australia (White RB, Thomas MG)
  • Received:2015-11-03 Online:2016-01-15 Published:2016-01-15
  • Contact: Robert B. White, Ph.D., robert.white@uwa.edu.au.

摘要:

细胞从发育最初阶段开始其时间和空间位置能够预测独特的生长因子组合,而这些组合因子会通过其特定的转录因子决定细胞内设置的转录平台。这反过来又决定了它们将分化成何种细胞类型?之间有什么使其链接?但这一发育平台如何转化为成人大脑中具有保护效应的特定神经元,目前还不太清楚。大多数发育因素能够控制分化过程期间和之后的各个方面:如DNA合成或增殖对分化神经元显然是没有什么作用,但其却能唤起破坏性影响。那么为什么成人大脑在应激、创伤和疾病过程中可以观察到发育因子上调现象?目前由两种可能的解释:首先,有一个细胞通道使用它“知道”的唯一机制尝试进行复原过程,或第二种,事实上这些转录因子不只是简单地“发育因子”,其在不同的情况下可以驱动不同的转录平台,即“术业有专攻”。当然这两种假设不一定是相互排斥的。尽管有许多发育转录因子编码基因因为招募“动机”在以后的环境中是否会存在生存困难的问题。文章表示Pax在脊椎动物与无脊椎动物发育过程中广泛表达,它们在胚胎发育过程中起着重要的调控作用。Pax基因表达的蛋白是一类重要的转录调控因子,Pax基因家族有九个成员,其中Pax6在生物生长发育中起到重要作用,它调节很多生命活动中的分子表达,包括转录因子、细胞粘附因子、短距离细胞-细胞信号分子、激素及结构蛋白等;它广泛参与细胞增殖、迁移、分化和粘附等生命活动,通过不同的剪接变异体与多种蛋白结合,在不同的组织和细胞中发挥不同的功能。Pax6是一个关键的神经性因子,是研究者们普遍接受的神经性原性决定因素。

Abstract:

The Pax6 gene belongs to the highly functionally and structurally conserved Pax gene family (Pax1–9) of tissue-specific transcription factors. The Pax family are instrumental in development and have a critical role in brain regionalisation and specification of subtypes of neurons within brain regions. Pax6 is one of the earliest gene products expressed in the developing embryo. Pax6 is a key neurogenic factor and a well-accepted neurogenic determinant. Indeed, Pax6 is frequently used as a marker of neural precursor status and recent studies have demonstrated that overexpression of both Pax6 and another transcription factor, Sox2, is sufficient to transdifferentiate fibroblast cells into induced neuronal progenitors (Maucksch et al., 2012), in line with it having been demonstrated that Pax6 alone induces neuronal specification of postnatal forebrain astrocytes.