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脑蛋白质组学将氧化应激与阿尔茨海默病模型大鼠行为改变中的代谢及细胞应激反应蛋白联系起来。

Brain proteomics links oxidative stress with metabolic and cellular stress response proteins in behavioural alteration of Alzheimer's disease model rats.

作者信息

Rahman Mohammad Azizur, Hossain Shahdat, Abdullah Noorlidah, Aminudin Norhaniza

机构信息

Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka, Bangladesh.

Mushroom Research Centre, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.

出版信息

AIMS Neurosci. 2019 Nov 15;6(4):299-315. doi: 10.3934/Neuroscience.2019.4.299. eCollection 2019.

DOI:10.3934/Neuroscience.2019.4.299
PMID:32341985
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7179348/
Abstract

Alzheimer's disease (AD) impairs memory and learning related behavioural performances of the affected person. Compared with the controls, memory and learning related behavioural performances of the AD model rats followed by hippocampal proteomics had been observed in the present study. In the eight armed radial maze, altered performance of the AD rats had been observed. Using liquid chromatography coupled tandem mass spectrometry (LC-MS/MS), 822 proteins had been identified with protein threshold at 95.0%, minimum peptide of 2 and peptide threshold at 0.1% FDR. Among them, 329 proteins were differentially expressed with statistical significance (P < 0.05). Among the significantly regulated (P < 0.05) 329 proteins, 289 met the criteria of fold change (LogFC of 1.5) cut off value. Number of proteins linked with AD, oxidative stress (OS) and hypercholesterolemia was 59, 20 and 12, respectively. Number of commonly expressed proteins was 361. The highest amount of proteins differentially expressed in the AD rats were those involved in metabolic processes followed by those linked with OS. Most notable was the perturbed state of the cholesterol metabolizing proteins in the AD group. Current findings suggest that proteins associated with oxidative stress, glucose and cholesterol metabolism and cellular stress response are among the mostly affected proteins in AD subjects. Thus, novel therapeutic approaches targeting these proteins could be strategized to withstand the ever increasing global AD burden.

摘要

阿尔茨海默病(AD)会损害患者与记忆和学习相关的行为表现。在本研究中,观察了海马蛋白质组学研究后的AD模型大鼠与记忆和学习相关的行为表现,并与对照组进行了比较。在八臂辐射状迷宫中,观察到AD大鼠的行为表现有所改变。使用液相色谱串联质谱法(LC-MS/MS),在蛋白质阈值为95.0%、最小肽段数为2且肽段阈值为0.1%错误发现率(FDR)的条件下,共鉴定出822种蛋白质。其中,有329种蛋白质存在显著差异表达(P < 0.05)。在这329种显著调控(P < 0.05)的蛋白质中,有289种满足倍数变化(LogFC为1.5)的截断值标准。与AD、氧化应激(OS)和高胆固醇血症相关的蛋白质数量分别为59种、20种和12种。共同表达的蛋白质数量为361种。AD大鼠中差异表达量最高的蛋白质是那些参与代谢过程的蛋白质,其次是与OS相关的蛋白质。最值得注意的是AD组中胆固醇代谢蛋白的紊乱状态。目前的研究结果表明,与氧化应激、葡萄糖和胆固醇代谢以及细胞应激反应相关的蛋白质是AD患者中受影响最大的蛋白质之一。因此,可以制定针对这些蛋白质的新型治疗方法,以应对日益增加的全球AD负担。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e30b/7179348/bf1d9eaf7d4b/neurosci-06-04-299-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e30b/7179348/681e5e0c8879/neurosci-06-04-299-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e30b/7179348/50fe76823400/neurosci-06-04-299-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e30b/7179348/70bad3863532/neurosci-06-04-299-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e30b/7179348/863c78c7e15b/neurosci-06-04-299-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e30b/7179348/bf1d9eaf7d4b/neurosci-06-04-299-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e30b/7179348/681e5e0c8879/neurosci-06-04-299-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e30b/7179348/50fe76823400/neurosci-06-04-299-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e30b/7179348/70bad3863532/neurosci-06-04-299-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e30b/7179348/863c78c7e15b/neurosci-06-04-299-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e30b/7179348/bf1d9eaf7d4b/neurosci-06-04-299-g005.jpg

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