Target Identification and Drug Repurposing for Parkinson's Disease: A NOVEL Integrative Computational Approach
Author(s)
Vithal Yergolkar A1, Yalamanchili J1, Satish K1, G N S HS2, Saraswathy GR3
1Department of Pharmacy Practice, Faculty of Pharmacy, M. S. Ramaiah University of Applied Sciences, Bangalore, KA, India, 2Pharmacological Modelling and Simulation Centre, M. S. Ramaiah University of Applied Sciences, Banglore, Karnataka, India, Bangalore, India, 3Department of Pharmacy Practice, Faculty of Pharmacy, M. S. Ramaiah University of Applied Sciences, Bangalore, India
OBJECTIVES Parkinson’s disease (PD) is a complex neurodegenerative disorder. With a multifactorial etiology, the pathological findings suggest cell death in the basal ganglia causing depletion of neurons secreting dopamine leading to motor and neuropsychiatric complications. Till date, there is no cure or treatment for PD that could reduce the progression of the disease. This startling situation demands rigorous research to identify drugs for the treatment of PD. The main objective of this study is to identify potential targets and repurpose the existing drugs for PD through in silico approach. METHODS The differentially expressed genes (DEGs) in the substantia nigra of patients with PD were retrieved from Gene Expression Omnibus (GEO) dataset GSE8397. Protein-Protein Interactions (PPI) network analysis was constructed for DEGs and targets with high combined score were selected along with druggable targets and their similar structures were obtained from Drug Repurposing Hub and DrugBank (DB) respectively for further docking studies and free binding energy (𝛥G) analysis using Schrodinger Glide and Prime tools. RESULTS A total of 19 DEGs were obtained with p value <0.05. The PPI network showed high interactions for B4GALT6, DCLK1, DENR, GNB5, KCNJ6, PDK4, RAB6B and SNCA. All these targets are reported for PD and were found in the dataset and docking studies were performed for suitable targets. Fostamatinib, Isavuconazole and Piceatannol had the highest docking scores against DCLK1, KCNJ6 and SNCA targets. Also those drugs were found to possess good CNS permeability and high 𝛥G values. CONCLUSION Our study concluded that DCLK1, KCNJ6 and SNCA are potential PD targets. Fostamatinib, Isavuconazole and Piceatannol could be repurposed for PD.
Conference/Value in Health Info
2020-09, ISPOR Asia Pacific 2020, Seoul, South Korea
Value in Health Regional, Volume 22S (September 2020)
Code
PND24
Topic
Methodological & Statistical Research
Disease
Neurological Disorders