Both the Formation and Polyphenol-Induced Dissociation of Various Amyloid Fibrils are Accompanied by ROS Formation

Abstract

Fibrillization of amyloid polypeptides is accompanied by formation of reactive oxygen species (ROS), which, in turn, is assumed to further promote amyloid-related pathologies. Different polyphenols, all of which are established antioxidants, cause dissociation of amyloid fibrils. In this study we address the latter, poorly understood process. Specifically, we have investigated the dissociation of Aβ42 fibrils by six different polyphenols, using electron microscopy and spectrofluorimetric analysis. Simultaneously, we have monitored the production of ROS using electron spin resonance (ESR) and the commercially available peroxide assay kit. Using the same methods, we found that curcumin, one of the most potent destabilizing agents of Aβ42, induces dissociation of fibrils of other amyloid polypeptides [Aβ40, Aβ42Nle35, islet amyloid polypeptide and a fragment of α-synuclein].When the solution contained traces of transition metal, all the dissociation reactions were accompanied by ROS formation, independent of the presence of a methionine residue. Kinetic studies show that the formation of ROS lags behind dissociation, indicating that if casual relationship exists between these two processes, then ROS formation may be considered a consequence and not a cause of dissociation.Understanding of our results and of their implications requires further research.