γ-Secretase Inhibitors Selected by Molecular Docking, to Develop a New Drug Against Alzheimer's Disease

Background: Alzheimer ' s disease (AD) is one of the most common forms of dementia, is characterized by memory loss and cognitive impairment that affects more than 30 million people worldwide. The pathogenesis of Alzheimer's disease is primary driven by brain accumulation of the amyloid 13 peptide generated from the amyloid-13 precursor protein (APP) via cleavages by 13- and gamma-secretase. In this study, we propose an approach by molecular docking to select compounds as gamma-secretase inhibitors for decreasing the APP generation. Methods: We selected potential gamma-secretase inhibitors by molecular docking in the potential site between Asp257, Lue268, Asp385, Ile387, Phe388, and Leu432 amino acids in presenilin-1 (PS-1), using a chemical library of over 500,000 compounds. Results: Eight compounds (AZ1 - AZ8) were selected by molecular docking to develop gamma-secretase inhibitors for decreasing the APP generation. Conclusion: AZ1 - AZ8 compounds could be interacting in the potential site between Asp257, Lue268, Asp385, Ile387, Phe388, and Leu432 amino acids in PS-1. These compounds could specifically interact in the binding pocket in PS-1 to prevent/decrease the APP generation, to develop a new drug against Alzheimer's disease.