AUTHOR=Eskandarzadeh Marzieh , Kordestani-Moghadam Parastou , Pourmand Saeed , Khalili Fard Javad , Almassian Bijan , Gharaghani Sajjad 

TITLE=Inhibition of GSK_3β by Iridoid Glycosides of Snowberry (Symphoricarpos albus) Effective in the Treatment of Alzheimer’s Disease Using Computational Drug Design Methods

JOURNAL=Frontiers in Chemistry

VOLUME=Volume 9 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2021.709932

DOI=10.3389/fchem.2021.709932

ISSN=2296-2646

ABSTRACT=Inhibition of GSK3_β activity prevents tau hyperphosphorylation and binds it to the microtubule network. Therefore, A GSK3_β inhibitor may be a recommended drug for the treatment of Alzheimer's. In silico methods are currently one of the fastest and most cost-effective methods available for drug design discovery in the field of treatment. In this study, we became interested in performing computational drug design to introduce compounds that play an effective role in inhibiting the GSK3_β enzyme by molecular docking and molecular dynamics simulation. Iridoid glycosides of the Common Snowberry (Symphoricarpos Albus), including loganin, Secologanin and loganetin, are compounds that have effects on improving memory and cognitive impairment, the results of which on Alzheimer's have also been studied. In this study, in the molecular docking phase, loganin was considered a more potent inhibitor of this protein by establishing a hydrogen bond with the GSK3_β protein ATP_binding site and the most negative binding energy to secologanin and loganetin. Beside on, by molecular dynamics simulation of these ligands and GSK3_β protein, all structures were found to be stable during the simulation, and by binding ligands to GSK3_β protein, the protein structure has not been changed and remained stable. Furthermore, Loganin had established stronger hydrogen bonds than loganetin and secologanin and was able to bind well to the active site of GSK3_β protein. Therefore, it can be concluded that loganin as an Iridoid glycoside can be effective in the prevention and treatment of Alzheimer's, and as an option treatment, further in vitro and in vivo studies can be performed on it.