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

AbstractParkinson ’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 ta rgets 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, andTAC1 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 noticedSYT1 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 miRNAsmiR-21,miR-155,miR-7, andmiR26A1 have a significant role in modulating the hub genes. Briefly, these significant hub genes and their enriched pathways,...
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research