Formation of protein amyloid aggregates is characteristic sign in many different human diseases. Amyloid aggregation of Aβ-peptide and accumulation of amyloid deposits in human brain is associated with Alzheimer's disease. We have investigated the anti-amyloid properties of fullerenol (C60-16(OH)), a water soluble derivative of fullerene C60 prepared by Solvent-Free Reaction described at Wang et al. 2005 [1], using in vitro and in silico methods.
The ability of fullerenol to inhibit Aβ peptide fibrillization was examined by ThT assay. Binding of ThT to assembled β-structures of amyloid fibrils leads to significant increasing of fluorescence intensity of ThT. The results indicate that fullerenol is able to inhibit fibrillization of Aβ peptide at stoichiometric concentrations with Aβ1-40 peptide (micromolar range).
The in silico data obtained by docking and MM/PBSA methods showed that fullerenol C60-16(OH) is tightly binding to monomer Aβ1-40. The theoretical calculations determined that for the fullerenol binding the side-chain contacts and van der Waals interaction are the most important
In this work was shown that fullerenol C60-16(OH) is able to prevent the formation of Aβ1-40 peptide amyloid fibrils and can be a promising candidate in search of therapeutics for Alzheimer's disease.
Acknowledgement: This work was supported by the research grants from Slovak Grant Agency VEGA 0181, UPJS grant VVGS-2013-98, the project ESF 26110230097 and APVV 0171-10.