Bioinformatics and System Biology Techniques to Determine Biomolecular Signatures and Pathways of Prion Disorder.

Abstract

Prion disorder (PD) is caused by misfolding and the formation of clumps of proteins in the brain, notably Prion proteins resulting in a steady decrease in brain function. Early detection of PD is difficult due to its unpredictable nature, and diagnosis is limited regarding specificity and sensitivity. Considering the uncertainties, the current study used network-based integrative system biology approaches to reveal promising molecular biomarkers and therapeutic targets for PD. In this study, brain transcriptomics gene expression microarray datasets (GSE160208 and GSE124571) of human PD were evaluated and 35 differentially expressed genes (DEGs) were identified. By employing network-based protein-protein interaction (PPI) analysis on these DEGs, 10 central hub proteins, including SPP1, FKBP5, HPRT1, CDKN1A, BAG3, HSPB1, SYK, TNFRSF1A, PTPN6, and CD44, were identified. Employing bioinformatics approaches, a variety of transcription factors (EGR1, SSRP1, POLR2A, TARDP, and NR2F1) and miRNAs (hsa-mir-8485, hsa-mir-148b-3p, hsa-mir-4295, hsa-mir-26b-5p, and hsa-mir-16-5p) were predicted. EGR1 was found as the most imperative transcription factor (TF), and hsa-mir-16-5p and hsa-mir-148b-3p were found as the most crucial miRNAs targeted in PD. Finally, resveratrol and hypochlorous acid were predicted as possible therapeutic drugs for PD. This study could be helpful in better understanding of molecular systems and prospective pharmacological targets for developing effective PD treatments.