Mechanistic study of the inhibition of monoamine oxidase-B by quercetin as the potential therapeutic strategy for Parkinson's Disease: An in silico approach

Parkinson's Disease (PD) is one of the most fatal neurodegenerative disease, characterized by the loss of dopaminergic neurons from the Substantia Nigra Pars Compacta (SNPC) of basal ganglia in brain. The loss of dopaminergic neurons is due to various cellular threats, among which, the oxidative stress is one of the major cause. The occurrence of oxidative stress is due to the activity of Monoamine oxidase-B, which generates reactive oxygen species (ROS) leading to DNA damage, resulting in apoptosis. On the other hand, in vivo studies revealed the potential effect of quercetin to inhibit MAO-B in brain. But the molecular mechanism of this inhibition is unclear. Here, we have studied the inhibitory mechanism of quercetin with MAO-B through in silico approach, where we have done molecular docking analysis of quercetin with MAO-B with the help of Autodock Vina and further studied the docked complex with the help of molecular dynamic simulation (MDS) studies using GROMACS 5.1.2. We found that the active sites of MAO-B are involved while interacting with quercetin, suggesting the potential inhibition of MAO-B. Moreover, the MDS study reveals that, the docked complex is more stable than free protein as the former contains more hydrogen bonds. The mechanistic understanding of the interaction between quercetin and MAO-B will generate new strategies to improve quercetin based drugs for inhibiting MAO-B and provides new scope for drug designing and discovery which potentially aids novel therapeutic strategies to combat PD.