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阿尔茨海默病患者大脑区域中蛋白质的差异表达。

Differential expression of proteins in brain regions of Alzheimer's disease patients.

机构信息

Neurochemistry Research Laboratory, Department of Biochemistry, University of Karachi, Karachi, 75270, Pakistan.

出版信息

Neurochem Res. 2014 Jan;39(1):208-15. doi: 10.1007/s11064-013-1210-1. Epub 2013 Dec 4.

Abstract

Alzheimer's disease (AD), a progressive neurodegenerative disorder and the most common form of dementia and cognitive impairment is usually characterized by neuritic amyloid plaques, cerebrovascular amyloidosis and neurofibrillary tangles. In order to find out the pathological protein expression, a quantitative proteome analysis of AD hippocampus, substantia nigra and cortex was performed and the extent of protein expression variation not only in contrast to age-matched controls but also among the understudied regions was analyzed. Expression alterations of 48 proteins were observed in each region along with significant co/contra regulation of malate dehydrogenase, lactate dehydrogenase B chain, aconitate hydratase, protein NipSnap homolog 2, actin cytoplasmic 1, creatine kinase U-type and glyceraldehyde-3-phosphate dehydrogenase. These differentially expressed proteins are mainly involved in energy metabolism, cytoskeleton integration, apoptosis and several other potent cellular/molecular processes. Interaction association network analysis further confirms the close interacting relationship between the co/contra regulated differentially expressed proteins among all the three regions. Elucidation of co/contra regulation of differentially expressed proteins will be helpful to understand disease progression and functional alterations associated with AD.

摘要

阿尔茨海默病(AD)是一种进行性神经退行性疾病,也是最常见的痴呆和认知障碍形式,通常以神经纤维缠结、脑血管淀粉样变性和神经原纤维缠结为特征。为了查明病理蛋白的表达情况,对 AD 海马体、黑质和皮质进行了定量蛋白质组分析,不仅分析了与年龄匹配的对照组相比的蛋白表达变化程度,还分析了在研究较少的区域中的蛋白表达变化程度。在每个区域中观察到 48 种蛋白的表达变化,同时还观察到苹果酸脱氢酶、乳酸脱氢酶 B 链、顺乌头酸酶、NipSnap 同源物 2、肌动蛋白细胞质 1、肌酸激酶 U 型和甘油醛-3-磷酸脱氢酶的显著协同/拮抗调节。这些差异表达的蛋白主要参与能量代谢、细胞骨架整合、细胞凋亡和其他几种有效的细胞/分子过程。相互作用关联网络分析进一步证实了所有三个区域中协同/拮抗调节的差异表达蛋白之间的密切相互关系。阐明差异表达蛋白的协同/拮抗调节将有助于了解与 AD 相关的疾病进展和功能改变。

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