阿尔茨海默病内嗅皮质关键基因的鉴定和药物再利用靶点。

IF 1.6 4区 医学 Q3 CLINICAL NEUROLOGY
Arghavan Hosseinpouri, Khadijeh Sadegh, Zeinab Zarei-Behjani, Zeinab Dehghan, Reza Karbalaei
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引用次数: 0

摘要

阿尔茨海默病(AD)是一种缓慢的脑变性疾病,其中β -淀粉样蛋白前体斑块的积累和大脑中过度磷酸化的tau蛋白的细胞内神经原纤维缠结与神经变性有关。在这项研究中,我们确定了大脑内嗅区独特而敏感的最重要基因,以有效地靶向AD。首先,选择微阵列数据,利用Cytoscape软件从差异表达基因(deg)中构建蛋白-蛋白相互作用网络(PPIN)和基因调控网络(GRN)。然后,进行网络分析以确定AD中的集线器、瓶颈、集群和信号通路。最后,选择关键基因作为药物再利用的靶点。分析构建的PPIN和GRN,发现CD44、ELF1、HSP90AB1、NOC4L、BYSL、RRP7A、SLC17A6和RUVBL2是AD患者内嗅区失调的关键基因。功能富集分析显示,DEG节点参与突触囊泡循环、谷氨酸能突触、PI3K-Akt信号通路、内源性大麻素逆行信号通路、内分泌等因子调控的钙重吸收、真核生物核糖体生物发生、尼古丁成瘾等。庆大霉素、异丙肾上腺素和肿瘤坏死因子正在重新利用靶向CD44的新药,CD44在AD的发展中起着重要作用。在使用现有实验数据验证我们的模型之后,我们的模型基于先前的实验报告,提出了参与AD的关键分子和候选药物,用于进一步的体外和体内研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification of critical genes and drug repurposing targets in entorhinal cortex of Alzheimer's disease.

Alzheimer's disease (AD) is a slow brain degeneration disorder in which the accumulation of beta-amyloid precursor plaque and an intracellular neurofibrillary tangle of hyper-phosphorylated tau proteins in the brain have been implicated in neurodegeneration. In this study, we identified the most important genes that are unique and sensitive in the entorhinal region of the brain to target AD effectively. At first, microarrays data are selected and constructed protein-protein interaction network (PPIN) and gene regulatory network (GRN) from differentially expressed genes (DEGs) using Cytoscape software. Then, networks analysis was performed to determine hubs, bottlenecks, clusters, and signaling pathways in AD. Finally, critical genes were selected as targets for repurposing drugs. Analyzing the constructed PPIN and GRN identified CD44, ELF1, HSP90AB1, NOC4L, BYSL, RRP7A, SLC17A6, and RUVBL2 as critical genes that are dysregulated in the entorhinal region of AD suffering patients. The functional enrichment analysis revealed that DEG nodes are involved in the synaptic vesicle cycle, glutamatergic synapse, PI3K-Akt signaling pathway, retrograde endocannabinoid signaling, endocrine and other factor-regulated calcium reabsorption, ribosome biogenesis in eukaryotes, and nicotine addiction. Gentamicin, isoproterenol, and tumor necrosis factor are repurposing new drugs that target CD44, which plays an important role in the development of AD. Following our model validation using the existing experimental data, our model based on previous experimental reports suggested critical molecules and candidate drugs involved in AD for further investigations in vitro and in vivo.

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来源期刊
Neurogenetics
Neurogenetics 医学-临床神经学
CiteScore
3.90
自引率
0.00%
发文量
24
审稿时长
6 months
期刊介绍: Neurogenetics publishes findings that contribute to a better understanding of the genetic basis of normal and abnormal function of the nervous system. Neurogenetic disorders are the main focus of the journal. Neurogenetics therefore includes findings in humans and other organisms that help understand neurological disease mechanisms and publishes papers from many different fields such as biophysics, cell biology, human genetics, neuroanatomy, neurochemistry, neurology, neuropathology, neurosurgery and psychiatry. All papers submitted to Neurogenetics should be of sufficient immediate importance to justify urgent publication. They should present new scientific results. Data merely confirming previously published findings are not acceptable.
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