ABSTRACT
One of the hallmarks of Alzheimer's Disease (AD) is the anomalous binding involving amyloid-ß (Aß) peptide and metal ions, such as copper, formed through histidine (His) residues. Herein, adsorption experiments were performed to test the in vitro ability of chitosan to uptake copper ions in the presence of histidine. The characterization of the beads was assessed before and after the adsorption process by scanning electron microscope, X-ray diffraction and Fourier-transform infrared spectroscopy. Amino acid functionalization of chitosan-based beads promoted an increase in the copper ions adsorption capacity (2.47 mmol of Cu(II)/gram of adsorbent). Nevertheless, depending on the order of addition of histidine to the system, different adsorption behaviors were observed. The kinetics showed that, once the Cu(II)-His bond was established, functionalized beads were less efficient to capture Cu(II), which promoted a decrease in the overall adsorption capacity. However, when chitosan and histidine were simultaneously added to the Cu(II) solution, there was no decrease in adsorption capacity. To sum up, chitosan-based materials are an interesting model to provide a better understanding on the biomoleculescopper interactions that occur in AD, as well as a possible chelating agent that can interfere in the bonds between Aß residues and copper ions.
Subject(s)
Amyloid beta-Peptides/chemistry , Chitosan/chemistry , Copper/chemistry , Histidine/chemistry , Adsorption/drug effects , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Amino Acids/chemistry , Chitosan/pharmacology , Humans , Ions/chemistry , Kinetics , Microscopy, Electron, Scanning , Spectroscopy, Fourier Transform Infrared , X-Ray DiffractionABSTRACT
Alzheimer's disease (AD) is related to the anomalous binding that occurs between amyloid-ß peptide (Aß) 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 Aß aggregation and Thioflavin T binding assay indicated that chitosan has affinity for Aß and interferes in its aggregation. We also tested the ability of Chi to uptake copper ions in the presence of Aß or His. Equilibrium data reveals that chitosan acted as an effective chelating agent competing with Aß and histidine for copper binding. The addition of histidine or Aß 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.