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首页> 外文期刊>Journal of Molecular Neuroscience: MN >Integrative Analysis of Gene Expression and Regulatory Network Interaction Data Reveals the Protein Kinase C Family of Serine/Threonine Receptors as a Significant Druggable Target for Parkinson's Disease
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Integrative Analysis of Gene Expression and Regulatory Network Interaction Data Reveals the Protein Kinase C Family of Serine/Threonine Receptors as a Significant Druggable Target for Parkinson's Disease

机译：基因表达和调节网络相互作用数据的整合分析显示丝氨酸蛋白激酶C系列丝氨酸/苏氨酸受体是帕金森病的重要可毒靶

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Parkinson's disease (PD) is a progressive neurodegenerative disease affecting the ventral midbrain dopaminergic neurons, resulting in motor defects mainly tremor, rigidity, and bradykinesia along with a wide array of non-motor symptoms. The current study is focused on determining the potential druggable targets of PD by consolidating gene expression profiling and network methodology. Initially, the differentially expressed genes were established from which the central network was constructed by assimilating the interacting partners. Investigating the topological parameters of the network, the genesSYT1,CXCR4,CDC42,KIT,RET,DRD2,NTN1,PRKACB,KDR,NR4A2,SLC18A2,CCK,TH,KCNJ6, andTAC1were identified as the hub genes and can be explored as potential candidate genes for PD therapeutics. Gene ontology and cluster analysis of the hub genes has provided further insights about the pathophysiology of the disease. Among the hub genes,PRKACBis observed in relatively all the enriched pathways which are modulated by G protein-coupled receptors through protein kinases. Further, we noticedSYT1as a novel biomarker for PD. Moreover, the regulatory network was constructed with the hub genes as seed nodes with associated transcription factors (TFs) and microRNA (miRNAs). In this analysis, we identified MYC as the major TF and the miRNAsmiR-21,miR-155,miR-7, andmiR26A1have a significant role in modulating the hub genes. Briefly, these significant hub genes and their enriched pathways, TFs, and miRNAs have aided in the better understanding of molecular mechanisms underlying PD and its potential core target genes.
机译：帕金森病（Parkinson’s disease，PD）是一种累进性神经退行性疾病，影响中脑腹侧多巴胺能神经元，导致运动缺陷，主要是震颤、强直和运动迟缓，以及各种非运动症状。目前的研究重点是通过整合基因表达谱和网络方法来确定PD的潜在药物靶点。最初，通过同化相互作用的伙伴，建立了差异表达基因，并由此构建了中心网络。通过对网络拓扑参数的研究，YT1、CXCR4、CDC42、KIT、RET、DRD2、NTN1、PRKACB、KDR、NR4A2、SLC18A2、CCK、TH、KCNJ6和TAC1基因被确定为中枢基因，可以作为PD治疗的潜在候选基因进行探索。hub基因的基因本体和聚类分析为该疾病的病理生理学提供了进一步的见解。在hub基因中，prkacb存在于相对所有的富集途径中，这些富集途径由G蛋白偶联受体通过蛋白激酶调节。此外，我们注意到SYT1是一种新的PD生物标志物。此外，调控网络是以hub基因为种子节点，结合相关转录因子（TFs）和microRNA（miRNAs）构建的。在这项分析中，我们确定MYC是主要的TF，而miRNAsmiR-21、miR-155、miR-7和miR-26A1在调节中枢基因方面具有重要作用。简而言之，这些重要的中枢基因及其富集途径、TFs和miRNA有助于更好地理解PD及其潜在核心靶基因的分子机制。

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