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RNA 聚合酶 III 转录及其调控在缺血性脑卒中中的作用。

Role of RNA polymerase III transcription and regulation in ischaemic stroke.

机构信息

Clinical Neuroscience Institute, The First Affiliated Hospital of Jinan University, Guangzhou, China.

Rutgers Cancer Institute, The State University of New Jersey, New Brunswick, NJ, USA.

出版信息

RNA Biol. 2024 Jan;21(1):1-10. doi: 10.1080/15476286.2024.2409554. Epub 2024 Oct 3.

Abstract

Ischaemic stroke is a leading cause of death and life-long disability due to neuronal cell death resulting from interruption of glucose and oxygen supplies. RNA polymerase III (Pol III)-dependent transcription plays a central role in protein synthesis that is necessary for normal cerebral neuronal functions, and the survival and recovery under pathological conditions. Notably, Pol III transcription is highly sensitive to ischaemic stress that is known to rapidly shut down Pol III transcriptional activity. However, its precise role in ischaemic stroke, especially during the acute and recovery phases, remains poorly understood. The microenvironment within the ischaemic brain undergoes dynamic changes in different phases after stroke. Emerging evidence highlights the distinct roles of Pol III transcription in neuroprotection during the acute phase and repair during the recovery phase of stroke. Additionally, investigations into the mTOR-MAF1 signalling pathway, a conserved regulator of Pol-III transcription, reveal its therapeutic potential in enhancing acute phase neuroprotection and recovery phase repair.

摘要

缺血性中风是导致死亡和终身残疾的主要原因,其原因是神经元细胞因葡萄糖和氧气供应中断而死亡。RNA 聚合酶 III(Pol III)依赖性转录在蛋白质合成中发挥核心作用,蛋白质合成是正常脑神经元功能所必需的,也是在病理条件下生存和恢复所必需的。值得注意的是,Pol III 转录对缺血应激非常敏感,已知其可迅速关闭 Pol III 转录活性。然而,其在缺血性中风中的确切作用,尤其是在急性和恢复阶段,仍知之甚少。中风后,缺血性大脑内的微环境在不同阶段会发生动态变化。新出现的证据强调了 Pol III 转录在中风急性阶段的神经保护和恢复阶段的修复中的独特作用。此外,对 mTOR-MAF1 信号通路(Pol-III 转录的保守调节剂)的研究揭示了其在增强急性阶段神经保护和恢复阶段修复方面的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f10f/11457610/09ada883931b/KRNB_A_2409554_F0001_OC.jpg

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