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热休克蛋白 70 家族成员是否会加重多发性硬化症的免疫反应?一项计算机模拟研究。

Could the Heat Shock Proteins 70 Family Members Exacerbate the Immune Response in Multiple Sclerosis? An in Silico Study.

机构信息

IRCCS Centro Neurolesi Bonino Pulejo, 98124 Messina, Italy.

出版信息

Genes (Basel). 2020 Jun 3;11(6):615. doi: 10.3390/genes11060615.

Abstract

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system. It represents one of the main causes of neurological disability in young people. In MS, the autoimmune response is directed against myelin antigens but other possible bio-molecular markers are investigated. The aim of this work was, through an in silico study, the evaluation of the transcriptional modifications between healthy subjects and MS patients in six brain areas (corpus callosum, hippocampus, internal capsule, optic chiasm, frontal and parietal cortex) in order to identify genes representative of the disease. Our results show the upregulation of the Heat Shock Proteins (HSPs) , , , , and of the HSP70 family, among which and are upregulated in all the brain areas. HSP70s are molecular chaperones indispensable for protein folding, recently associated with immune system maintenance. The little overexpression of the HSPs protects the cells from stress but extreme upregulation can contribute to the MS pathogenesis. We also investigated the genes involved in the immune system that result in overall upregulation in the corpus callosum, hippocampus, internal capsule, optic chiasm and are absent in the cortex. Interestingly, the genes of the immune system and the HSP70s have comparable levels of expression.

摘要

多发性硬化症(MS)是一种中枢神经系统的慢性自身免疫性脱髓鞘疾病。它是年轻人神经功能障碍的主要原因之一。在 MS 中,自身免疫反应针对髓鞘抗原,但也研究了其他可能的生物分子标志物。这项工作的目的是通过计算研究,评估 6 个大脑区域(胼胝体、海马体、内囊、视交叉、额叶和顶叶皮质)中健康受试者和 MS 患者之间的转录变化,以识别疾病的代表性基因。我们的结果表明,热休克蛋白(HSPs) 、 、 、 、 和 HSP70 家族的 上调,其中 和 在所有大脑区域都上调。HSP70s 是蛋白质折叠所必需的分子伴侣,最近与免疫系统的维持有关。HSPs 的轻度过表达可以保护细胞免受应激,但过度上调可能有助于 MS 的发病机制。我们还研究了参与免疫系统的基因,这些基因在胼胝体、海马体、内囊、视交叉中总体上调,而在皮质中不存在。有趣的是,免疫系统基因和 HSP70s 的表达水平相当。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3095/7348765/4fc661b549fc/genes-11-00615-g001.jpg

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