Identification of Hub Genes and Potential Molecular Pathogenesis in Substantia Nigra in Parkinson’s Disease via Bioinformatics Analysis

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease, with significant socioeconomic burdens. One of the crucial pathological features of PD is the loss of dopaminergic neurons in the substantia nigra (SN). However, the exact pathogenesis remains unknown. Moreover, therapies to prevent neurodegenerative progress are still being explored. We performed bioinformatics analysis to identify candidate genes and molecular pathogenesis in the SN of patients with PD. We analyzed the expression profiles, GSE49036 and GSE7621, which included 31 SN tissues in $\mathrm{P}\mathrm{D}\mathrm{s}\mathrm{a}\mathrm{m}\mathrm{p}\mathrm{l}\mathrm{e}\mathrm{s}\mathrm{a}\mathrm{n}\mathrm{d}17$ SN tissues in healthy control samples, and identified 86 common differentially expressed genes (DEGs). Then, GO and KEGG pathway analyses of the identified DEGs were performed to understand the biological processes and significant pathways of PD. Subsequently, a protein-protein interaction network was established, with 15 hub genes and four key modules which were screened in this network. The expression profiles, GSE8397 and GSE42966, were used to verify these hub genes. We demonstrated a decrease in the expression levels of 14 hub genes in the SN tissues of PD samples. Our results indicated that, among the 14 hub genes, DRD2, SLC18A2, and SLC6A3 may participate in the pathogenesis of PD by influencing the function of the dopaminergic synapse. CACNA1E, KCNJ6, and KCNB1 may affect the function of the dopaminergic synapse by regulating ion transmembrane transport. Moreover, we identified eight microRNAs (miRNAs) that can regulate the hub genes and 339 transcription factors (TFs) targeting these hub genes and miRNAs. Subsequently, we established an mTF-miRNA-gene-gTF regulatory network. Together, the identification of DEGs, hub genes, miRNAs, and TFs could provide better insights into the pathogenesis of PD and contribute to the diagnosis and therapies.