A Multi-target Study of Natural Compounds in Preventing Neurodegenerative Disease Progression: A Computational Modeling Study

Abstract

This work reveals how two natural multi-target compounds (Carnosine and Homocarnosine) can prevent the oligomerization of beta-amyloid peptides (A[Formula: see text]. Properly combining molecular dynamics, docking and electronic structure calculations it was possible to investigate how Carnosine/Homocarnosine strongly interact with the amino acids of the A[Formula: see text](1-42) peptide responsible for the complexation with metallic ions (metallic hypothesis). This discovery may prevent the formation of harmful protein deposits, thereby preventing the progression of, for example, Alzheimer’s disease (AD). These important results suggest that Carnosine/Homocarnosine can interact with, at least, two of the amino acids responsible for the complexation of the A[Formula: see text](1-42) peptide with the metallic ion copper(II). These findings open a new perspective on the inhibitory potential of these molecules in the treatment of AD and other neurodegenerative diseases.