Role of PARK7 and Linked Parkinsonism in Pakistani Population

Abstract

Parkinson’s disease (PD) is an idiopathic neurodegenerative disorder targeting seven to ten million of the elderly population. The PARK7 mutation trigger the loss of DJ-1 protein leading towards the early onset of PD. Objective: Our study aims to identify the PARK7 protein interactions and its potent interacting inhibitor by implying various bioinformatic tools. Methodology: In the present study, expression analysis was performed to determine the PARK7 gene expression levels in the CSF of PD patients. Then a detail spectrum analysis was performed for the quantification of the PARK7 protein fragment. Further, the ligand interactions of the PARK7 protein and α-synuclein were studied through LIGPLOT. Several bioinformatic tools were employed to study the protein-protein interactions along with post-translational modifications. Lastly, the technique of molecular docking was implied to detect the potent MAO-B inhibitor of the PARK7 protein. Results: Our study demonstrated modified expression levels of the PARK7 protein. The PARK7 expression analysis displayed the P value of 0.0106 in healthy versus sporadic PD. While healthy versus genetic PD exhibited the P value of 0.0013. Our detailed spectrum analysis illustrated 13 percent sequence coverage for the PARK7_HUMAN across the MS sample. Further, this research introduced three biological replicates: (K) VTVAGLAGK(D);(K) VTTHPLAK(D)& (K) DGLILTSR(G) with 100%; 99%& 99% probabilities, respectively. Moreover, the docking results suggested Safinamide with -5.4492 best energy score to be more potent interacting inhibitor as compared to Selegiline and Rasagiline. Conclusion: Outcome of this study, offers early characterization and targeting of proteins enabling effective diagnosis of PD. These investigations will aid in the discovery of alpha synuclein and MAO-B related inhibitors which reduced the effects of PD triggered by the PARK7 protein.