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 genes SYT1, CXCR4, CDC42, KIT, RET, DRD2, NTN1, PRKACB, KDR, NR4A2, SLC18A2, CCK, TH, KCNJ6, and TAC1 were 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, PRKACB is observed in relatively all the enriched pathways which are modulated by G protein-coupled receptors through protein kinases. Further, we noticed SYT1 as 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 miRNAs miR-21, miR-155, miR-7, and miR26A1 have 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.

帕金森病 (PD) 是一种进行性神经退行性疾病，影响腹侧中脑多巴胺能神经元，导致运动缺陷，主要是震颤、僵硬和运动迟缓以及一系列非运动症状。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，建立了差异表达的基因，从中构建了中心网络。调查网络的拓扑参数，基因SYT1，CXCR4，CDC42，KIT，RET，DRD2，NTN1，PRKACB、KDR、NR4A2、SLC18A2、CCK、TH、KCNJ6和TAC1被确定为中心基因，可以作为 PD 治疗的潜在候选基因进行探索。枢纽基因的基因本体论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在相对所有由G蛋白偶联受体通过蛋白激酶调节的富集途径中观察到。此外，我们注意到SYT1作为 PD 的新型生物标志物。此外，调控网络是用枢纽基因作为种子节点构建的，具有相关的转录因子（TFs）和微RNA（miRNAs）。在该分析中，我们将 MYC 确定为主要 TF，并且 miRNA miR-21、miR-155、miR-7和miR26A1在调节中枢基因方面具有重要作用。简而言之，这些重要的枢纽基因及其丰富的通路、TF 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。