How wine polyphenols can fight Alzheimer disease progression: towards a molecular explanation

Abstract

The present study provides clues at a molecular level towards an understanding of the mechanism of action of wine polyphenols on the protein Tau, whose aberrant phosphorylations are responsible for Alzheimer disease progression. Ten different flavan-3-ols that cover their natural structural diversity were tested with regard to their aptitude to fix a representative peptide of the proline-rich region of Tau (Gly 201-Thr 220) by using NMR and dynamic molecular modelling. The combination of these two techniques allows to locate the fixation sites: the fixation occurs in the peptide region where phosphorylations usually take place. The affinity was evaluated by titration curves and has been shown to depend on the presence of some procyanidin structural elements. Notably the presence of a galloyl moiety and the degree of polymerization are shown to increase the affinity. An ambivalence role of procyanidins has been evidenced: dynamic molecular data shows that they can play indifferently the role of hydrogen bond donor or acceptor.