在小鼠脑卒中模型中神经退行性疾病相关蛋白的动态变化和定位错误。

Dynamic changes and mislocalizations of neurodegenerative disease-related proteins in mice stroke model.

机构信息

Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kitaku, Okayama 700-8558, Japan.

出版信息

Brain Res. 2020 Sep 1;1742:146862. doi: 10.1016/j.brainres.2020.146862. Epub 2020 Apr 28.

DOI:10.1016/j.brainres.2020.146862

PMID:32360098

Abstract

The aggregation and cellular mislocalization of several RNA-binding proteins (RBPs) have been identified as the major hallmarks of neurodegenerative diseases such as frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). However, it remains obscure whether these pathological changes also occur during cerebral ischemia. In this study, we report that RBPs increased significantly compared with the sham group (*p < 0.05 and p < 0.01 vs sham), with nuclear depletion and cytoplasmic deposition in neurons in the acute phase of cerebral ischemia. On the other hand, such nucleocytoplasmic mislocalization were not observed in astrocytes. We provide evidence of the alteration of these neurodegeneration-related RBPs after cerebral ischemia, suggesting a potential association between cerebral ischemia and neurodegenerative diseases.

摘要

几种 RNA 结合蛋白（RBPs）的聚集和细胞定位错误已被确定为神经退行性疾病的主要特征，如额颞叶痴呆（FTD）和肌萎缩侧索硬化症（ALS）。然而，这些病理变化是否也发生在脑缺血期间尚不清楚。在这项研究中，我们报告说，与假手术组相比，RBPs 显著增加（*p < 0.05 和 p < 0.01 与假手术组相比），在脑缺血的急性期，神经元中出现核内耗竭和细胞质沉积。另一方面，在星形胶质细胞中没有观察到这种核质定位错误。我们提供了脑缺血后这些与神经退行性疾病相关的 RBPs 改变的证据，表明脑缺血与神经退行性疾病之间存在潜在的关联。