Alzheimer's disease (AD) is a debilitating condition that affects memory and behavior, typically in older individuals. Among the conjectures for AD causes, the so-called metallic hypothesis is still a topic of ongoing research and debate. It suggests that exposure to specific metallic ions like zinc, copper, and iron may contribute to the development of the disease. In this study, we investigate how using molecular docking, two natural compounds (Carnosine and Homocarnosine) may prevent the oligomerization of amyloid-beta (Abeta) peptides. Our findings reveal that these multi-target molecules strongly interact with the amino acids of the Abeta(1-42) peptide responsible for the complexation with metal ions, which can prevent the formation of harmful protein deposits (thus preventing AD progression). The results suggest that Carnosine and Homocarnosine could interact with, at least, two of the amino acids responsible for the complexation of the Abeta(1-42) peptide with the copper(II) metal ion. This study provides new insights into these compounds' potential in AD treatments.
Computational and theoretical techniques
All molecular docking simulations were performed by using the AutoDock computational code which includes the Lamarckian genetic algorithm. The ligands and the macromolecule were prepared by employing Gasteiger’s partial charge method based on empirical calculations of electronegativity equilibrium. The identification of patterns of hydrogen bonds and hydrophobic interactions between ligand-protein complexes was performed using LigPlot+ software.