QUERCETIN MODULATES AMYLOID-BETA AGGREGATION IN ALZHEIMER’S DISEASE: A MOLECULAR DYNAMICS SIMULATION APPROACH

Abstract

“Alzheimer's’ disease is an increasingly widespread ‘neurotoxic’ disease. It is characterized by a breakdown in brain transmission and cognitive decline. The condition is primarily driven by the abnormal accumulation of misfolded ‘amyloid beta’ clusters. There are several types of amyloid beta, but the two most neurotoxic and physiologically responsive are senile plaques with isoforms ‘Ab42’ and ‘Ab40’. Since these amyloid-beta senile plaques are crucial in the development of neurodegeneration, their inhibition is crucial for the fight against Alzheimer's disease. The neuroprotective and antioxidant properties of plant secondary metabolites, particularly flavonoids, have recently come to the forefront of scientific inquiry. Some research suggests that quercetin may inhibit the production of amyloid and effectively control oxidative stress. We used molecular dynamics simulations to learn more about the interactions between quercetin and the targeted Ab42 fibril in this study. We used the CHARMM27 force field for performing molecular dynamics simulations. Different analysis including ‘Hydrogen bond analysis’, ‘RMSD’, ‘RMSF’, ‘SASA’, and ‘DSSP’ were performed. Analysis of the radius of gyration shows that quercetin binding improves structural compactness and decreases conformational variations. The molecular level connection between quercetin and ‘Ab42 fibrils’ are explained in this paper, which also provides evidence to quercetin's therapeutic potential as a drug that can prevent Ab42 aggregation.