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轻度认知障碍患者血浆蛋白质组学生物标志物的鉴定

Identification of Plasma Proteomic Biomarkers in Patients with Mild Cognitive Impairment.

作者信息

Singh Vineeta, Mishra Vijaya Nath, Thakur Mahendra Kumar

机构信息

Department of Neurology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, UP 221005 India.

Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, UP 221005 India.

出版信息

Indian J Clin Biochem. 2023 Jan;38(1):33-41. doi: 10.1007/s12291-022-01023-1. Epub 2022 Feb 15.

Abstract

Plasma proteomic profiling may provide novel biomarkers for the identification of mild cognitive impairment (MCI). The early diagnosis of MCI still remains a challenging task due to its diverse origin. Currently, molecular approaches have been used to identify MCI diversified origin as its onset is governed by a variety of molecular changes. Therefore, we aimed to find out molecular alteration in plasma using proteomics in patients with MCI for early detection of prodromal Alzheimer's disease (AD). To achieve this, we performed two-dimensional (2-D) gel electrophoresis coupled with MALDI-TOF/MS, which is used to analyze the differentially expressed proteins. In our study, we found three significantly altered proteins. Out of three differentially expressed proteins, one was downregulated and two were upregulated in MCI individuals as compared to control. Further, In silico analysis showed that identified proteins are involved in pathways such as complement and coagulation cascades, platelet activation and AD. STRING interaction network analysis revealed that the majority of proteins including apolipoprotein E (APO-E) have a common association with Transthyretin (TTR) and fibrinogen chain beta (FGB) protein. This suggests that APO-E, TTR and FGB are the key proteins with which other proteins interact to exert other biological functions. Conclusively, these proteins showing differential expression in the plasma might be used as a potent signature in blood for the diagnosis of MCI individuals.

摘要

血浆蛋白质组学分析可为轻度认知障碍(MCI)的识别提供新的生物标志物。由于MCI起源多样,其早期诊断仍然是一项具有挑战性的任务。目前,分子方法已被用于识别MCI的多样起源,因为其发病受多种分子变化的支配。因此,我们旨在利用蛋白质组学研究MCI患者血浆中的分子改变,以早期检测前驱性阿尔茨海默病(AD)。为实现这一目标,我们进行了二维(2-D)凝胶电泳结合基质辅助激光解吸电离飞行时间质谱(MALDI-TOF/MS),用于分析差异表达的蛋白质。在我们的研究中,我们发现了三种显著改变的蛋白质。与对照组相比,在MCI个体中,三种差异表达的蛋白质中有一种下调,两种上调。此外,计算机分析表明,鉴定出的蛋白质参与补体和凝血级联反应、血小板活化和AD等途径。STRING相互作用网络分析显示,包括载脂蛋白E(APO-E)在内的大多数蛋白质与甲状腺素运载蛋白(TTR)和纤维蛋白原β链(FGB)蛋白有共同关联。这表明APO-E、TTR和FGB是关键蛋白质,其他蛋白质与其相互作用以发挥其他生物学功能。总之,这些在血浆中表现出差异表达的蛋白质可能作为诊断MCI个体的有力血液标志物。

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Sci Rep. 2019 Dec 10;9(1):18691. doi: 10.1038/s41598-019-55318-0.
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