NeuroAging Group (NEURAL), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain.
Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, La Paz University Hospital, Neuroscience Area of IdiPAZ Health Research Institute, Universidad Autónoma de Madrid, 28046 Madrid, Spain.
Int J Mol Sci. 2022 Mar 29;23(7):3747. doi: 10.3390/ijms23073747.
Ischemic stroke is a leading cause of death and disability worldwide. Following an ischemic insult, cells undergo endoplasmic reticulum (ER) stress, which increases the ER's protein-folding and degradative capacities and blocks the global synthesis of proteins by phosphorylating the eukaryotic translation initiation factor 2-alpha (eIF2α). Phosphorylation of eIF2α is directly related to the dynamics of stress granules (SGs), which are membraneless organelles composed of RNA-binding proteins and mRNA. SGs play a critical role in mRNA metabolism and translational control. Other translation factors are also linked to cellular pathways, including SG dynamics following a stroke. Because the formation of SGs is closely connected to mRNA translation, it is interesting to study the relationship between SG dynamics and cellular outcome in cases of ischemic damage. Therefore, in this review, we focus on the role of SG dynamics during cerebral ischemia.
缺血性中风是全球范围内导致死亡和残疾的主要原因。在缺血性损伤后,细胞会经历内质网(ER)应激,这会增加 ER 的蛋白质折叠和降解能力,并通过磷酸化真核翻译起始因子 2-α(eIF2α)来阻断蛋白质的全球合成。eIF2α 的磷酸化与应激颗粒(SGs)的动态直接相关,应激颗粒是由 RNA 结合蛋白和 mRNA 组成的无膜细胞器。SGs 在 mRNA 代谢和翻译控制中发挥着关键作用。其他翻译因子也与细胞途径有关,包括中风后 SG 的动态变化。由于 SG 的形成与 mRNA 翻译密切相关,因此研究 SG 动力学与缺血性损伤中细胞结果之间的关系很有趣。因此,在这篇综述中,我们重点关注脑缺血期间 SG 动力学的作用。