alpha-Synuclein (alpha syn) fibril formation is considered a central event in the pathogenesis of Parkinson's disease (PD). In recent years, it has been proposed that prefibrillar annular oligomeric beta-sheet-rich species, called protofibrils, rather than fibrils themselves, may be the neurotoxic species. The oxidation products of dopamine (DAQ) can inhibit alpha syn fibril formation supporting the idea that DAQ might stabilize asyn protofibrils. In the present work, through different biochemical and biophysical techniques, we isolated and structurally characterized alpha syn/DAQ adducts. Contrary to protofibrils, we demonstrated that alpha syn/DAQ adducts retain an unfolded conformation. We then investigated the nature of the modifications induced on asyn by DAQ. Our results indicate that only a small fraction of alpha syn interacts with DAQ in a covalent way, so that non-covalent interaction appears to be the major modification induced by DAQ on alpha syn. (C) 2010 Elsevier Inc. All rights reserved.