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帕金森病中 mRNA 和基因表达谱的综合网络分析。

An Integrated Network Analysis of mRNA and Gene Expression Profiles in Parkinson's Disease.

机构信息

Department of Neurology, Tianjin First Central Hospital, Tianjin, China (mainland).

出版信息

Med Sci Monit. 2020 Mar 25;26:e920846. doi: 10.12659/MSM.920846.

Abstract

BACKGROUND Parkinson's disease (PD) is a degenerative neurologic disease. This study aimed to undertake bioinformatics analysis using the publicly available Gene Expression Omnibus (GEO) database to integrate mRNA expression data from patients with PD and to compare differentially expressed genes (DEGs) in tissue from the substantia nigra and whole blood from patients with PD and normal controls. MATERIAL AND METHODS Integrated network analysis included GEO datasets to identify DEGs in the substantia nigra and whole blood of patients with PD. Bioinformatics analysis was used to identify the roles of the DEGs and included the development of protein-protein interaction (PPI) networks and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Expression levels of DEGs were validated using GSE100054. RESULTS In patients with PD, there were 1,076 upregulated DEGs and 1,075 down-regulated DEGs in the substantia nigra tissue, and 699 upregulated and 930 down-regulated DEGs in whole blood samples. The apoptotic process, the mitogen-activated protein kinase (MAPK) signaling pathway, the Wnt signaling pathway, and the Notch signaling pathway were significantly enriched in DEGs in the substantia nigra in PD. In both the substantia nigra and whole blood, the most common DEGs were significantly enriched in lysosomes, PD, Alzheimer's disease, Huntington's disease. SORT1 and CRYAB were the hub proteins in the network of the substantia nigra; PSMA1 and SDHA were the hub proteins in the network of whole blood in PD. CONCLUSIONS DEGs, including SORT1, CRYAB, PSMA1, and SDHA may have roles in the pathogenesis of PD through the MAPK, Wnt, and Notch signaling pathways.

摘要

背景

帕金森病(PD)是一种退行性神经疾病。本研究旨在利用公共可用的基因表达综合数据库(GEO)进行生物信息学分析,整合 PD 患者的组织中差异表达基因(DEGs)和 PD 患者及正常对照者全血中的差异表达基因。

材料与方法

综合网络分析包括 GEO 数据集,以确定 PD 患者黑质和全血中的 DEGs。生物信息学分析用于鉴定 DEGs 的作用,包括蛋白质-蛋白质相互作用(PPI)网络和京都基因与基因组百科全书(KEGG)通路的富集。使用 GSE100054 验证 DEGs 的表达水平。

结果

PD 患者黑质组织中上调的 DEGs 有 1076 个,下调的 DEGs 有 1075 个,全血样本中上调的 DEGs 有 699 个,下调的 DEGs 有 930 个。凋亡过程、丝裂原激活蛋白激酶(MAPK)信号通路、Wnt 信号通路和 Notch 信号通路在 PD 患者黑质中的 DEGs 中显著富集。在黑质和全血中,最常见的 DEGs 在溶酶体、帕金森病、阿尔茨海默病、亨廷顿病中显著富集。SORT1 和 CRYAB 是黑质网络中的枢纽蛋白;PSMA1 和 SDHA 是 PD 全血网络中的枢纽蛋白。

结论

包括 SORT1、CRYAB、PSMA1 和 SDHA 在内的 DEGs 可能通过 MAPK、Wnt 和 Notch 信号通路在 PD 的发病机制中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd54/7115122/9208122ebe93/medscimonit-26-e920846-g001.jpg

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