Unravelling Parkinson’s Disease Therapeutics: Computational Insights into VPS35 via Drug Repurposing

Parkinson’s disease (PD), is a neurodegenerative movement disorder that is characterized by dopaminergic loss. For getting deeper insights into the molecular and cellular mechanism underlying Parkinson’s, studies have now been focused on the genes for the cases that can have genetic origin. The novel cause of a dominant familial form of this disease has been found to defect in the vacuolar protein sorting (VPS35) gene. It is located on chromosome 16. AspD620Asn (D620N), a single missense mutation has been linked to the disease. Deficit of this protein can cause problems with autophagy and lysosomal process. Since VPS35 is involved in Parkinson’s disease, it may be a target for therapy. Docking of 3,674 FDA-approved drugs can be done along with reference drugs as a control to find better drugs with greater affinity. Based on their docking scores, three possible candidates were found after docking tirilazad, irinotecan, and alectinib. ADME analysis, which offers details on BBB permeability, water solubility, and bioavailability, was carried out for the validation of these compounds.