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en γ-Secretase Inhibitors Selected by Molecular Docking, to Develop a New Drug Against Alzheimer's Disease زیست شناسی ملکولی Molecular Biology مقالات اصلی Original Article <div style="text-align: justify;">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 β peptide generated from the amyloid-β precursor protein (APP) via cleavages by β- and γ-secretase. In this study, we propose an approach by molecular docking to select compounds as γ-secretase inhibitors for decreasing the APP generation. Methods: We selected potential γ-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 γ-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.</div> Amyloid Beta-Protein Precursor, Amyloid Precursor Protein Secretases, Alzheimer’s disease, Molecular Docking Simulation, Presenilin-1. 340 349 http://rbmb.net/browse.php?a_code=A-10-1044-2&slc_lang=en&sid=1 Carlos Humverto Trasviña-Arenas 100319475328460017987 100319475328460017987 Yes Research Center on Aging, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV), Calzada de los Tenorios No. 235, 14330, Mexico City, Mexico. Luis Alejandro Ayala Medina 100319475328460017988 100319475328460017988 No School of Medicine Campus Mexicali, Autonomous University of Baja California, Mexicali, 21000, BC, México. Jose Luis Vique-Sanchez jvique@uabc.edu.mx 100319475328460017989 100319475328460017989 No School of Medicine Campus Mexicali, Autonomous University of Baja California, Mexicali, 21000, BC, México.