In silico Analysis of caffeine effects on NMDA receptor in Alzheimer’s disease

Introduction: NMDAR is a glutamate receptor on the surface of neurons that acts as an ionic receptor. In the second phase of Alzheimer's disease (AD), the oligomer peptide of Beta-amyloid activates the downstream signaling pathway by binding to this receptor which leads to cell apoptosis. Studies have shown that inhibiting this receptor in AD patients can prevent the destruction of nerve cells. Caffeine in coffee and its effect on Alzheimer's disease has been known in the early stages of AD. We investigated the inhibitory effect of caffeine and its primary metabolites on NMDAR through computer simulated docking analysis.Materials and methods: Molecular docking is one of the structure-based computational methods used in drug design. In this study, we selected the structure of the NMDAR using PDB database. Caffeine, Paraxanthine, Theophylline, Theobromine, and a known NMDAR inhibitor called Memantine were used. The molecular docking process was performed using Molegro Virtual Docker V6.0 software. The results of docking based on bond free energy (Delta G) are investigated.Results: The comparative activity of caffeine, its primary metabolites and Memantine were analyzed by docking score and binding energy. The MolDock score of Caffeine, Paraxanthine, Theophylline, Theobromine and Memantine is -71.7622, -67.6633, -74.667, -72.6754 and -69.7672 kcal/mol respectively.Conclusion: Our results indicate the lower free binding energy and stronger binding affinity of caffeine and its primary metabolites to NMDAR compared to Memantine as a standard drug for AD. Therefore, it can be suggested that Caffeine has better inhibitory effects on NMDAR. In conclusion, this study shows the importance of natural small molecule screening and their use for an efficient drug discovery process.

کلیدواژه ها:

Alzheimer's disease ، NMDAR ، Molecular docking ، Molegro ، Memantine ، Caffeine