Copper Ion Uptake by Chitosan in the Presence of Amyloid-β and Histidine.

Alzheimer's disease (AD) is related to the anomalous binding that occurs between amyloid-β peptide (Aβ) and copper ion, through imidazole ring of histidine (His), as stated in the literature. It is also known that high-affinity metal ion chelators can be pharmacologically used as a possible therapeutic approach. In this work, we tested the ability "in vitro" of chitosan (Chi) to reduce Aβ aggregation and Thioflavin T binding assay indicated that chitosan has affinity for Aβ and interferes in its aggregation. We also tested the ability of Chi to uptake copper ions in the presence of Aβ or His. Equilibrium data reveals that chitosan acted as an effective chelating agent competing with Aβ and histidine for copper binding. The addition of histidine or Aβ in the system promotes an unfolding of chitosan chains, as verified by small-angle X-ray scattering. Extended X-ray absorption fine structure and XPS spectra show that new copper interactions with groups containing nitrogen in the presence of histidine may occur. These results can help understanding fundamental chemical interactions among species detected in AD and biopolymers, opening up possibilities for new treatment approaches for this disease.