DeGracia Donald J
Department of Physiology, Wayne State University, Detroit, MI, USA.
Wiley Interdiscip Rev RNA. 2017 Jul;8(4). doi: 10.1002/wrna.1415. Epub 2017 Jan 17.
There is growing appreciation that mRNA regulation plays important roles in disease and injury. mRNA regulation and ribonomics occur in brain ischemia and reperfusion (I/R) following stroke and cardiac arrest and resuscitation. It was recognized over 40 years ago that translation arrest (TA) accompanies brain I/R and is now recognized as part of the intrinsic stress responses triggered in neurons. However, neuron death correlates to a prolonged TA in cells fated to undergo delayed neuronal death (DND). Dysfunction of mRNA regulatory processes in cells fated to DND prevents them from translating stress-induced mRNAs such as heat shock proteins. The morphological and biochemical studies of mRNA regulation in postischemic neurons are discussed in the context of the large variety of molecular damage induced by ischemic injury. Open issues and areas of future investigation are highlighted. A sober look at the molecular complexity of ischemia-induced neuronal injury suggests that a network framework will assist in making sense of this complexity. The ribonomic network sits between the gene network and the various protein and metabolic networks. Thus, targeting the ribonomic network may prove more effective at neuroprotection than targeting specific molecular pathways, for which all efforts have failed to the present time to stop DND in stroke and after cardiac arrest. WIREs RNA 2017, 8:e1415. doi: 10.1002/wrna.1415 For further resources related to this article, please visit the WIREs website.
人们越来越认识到，信使核糖核酸（mRNA）调控在疾病和损伤中发挥着重要作用。mRNA调控和核糖组学发生在中风后的脑缺血再灌注（I/R）以及心脏骤停和复苏过程中。40多年前就已认识到，翻译停滞（TA）伴随脑I/R出现，现在被认为是神经元中触发的内在应激反应的一部分。然而，神经元死亡与注定要经历延迟性神经元死亡（DND）的细胞中延长的TA相关。注定要发生DND的细胞中mRNA调控过程的功能障碍会阻止它们翻译应激诱导的mRNA，如热休克蛋白。在缺血性损伤诱导的多种分子损伤的背景下，讨论了缺血后神经元中mRNA调控的形态学和生化研究。突出了未解决的问题和未来研究的领域。冷静审视缺血诱导的神经元损伤的分子复杂性表明，网络框架将有助于理解这种复杂性。核糖组网络位于基因网络与各种蛋白质和代谢网络之间。因此，与针对特定分子途径相比，靶向核糖组网络可能在神经保护方面更有效，目前针对特定分子途径的所有努力都未能阻止中风和心脏骤停后的DND。WIREs RNA 2017, 8:e1415. doi: 10.1002/wrna.1415 有关本文的更多资源，请访问WIREs网站。
