To address this issue, we previously performed experiments using single-particle fluorescence techniques, which allow distinguishing between monomer and oligomer binding to membranes. By this approach, we were able to demonstrate that asyn binding to lipid vesicles inhibits oligomer formation, whereas oligomers show enhanced binding to lipid membranes and may act as membrane pores. These data Pilocarpine nitrate salt further substantiate the hypothesis that interactions of asyn oligomers with cellular membranes are the key toxic event in synucleinopathies. Another ongoing controversy concerns the role of asyn phosphorylation in neurotoxicity. Phosphorylation at Ser129 is abundant in Lewy bodies, while the phosphorylation rate of asyn at this position appears to be low in the healthy mammalian brain. To date, both pro- and antiaggregatory effects of asyn phosphorylation and phosphorylation- mimicking mutations have been observed in vitro and in animal models. However, the role of asyn phosphorylation is not PET-cGMP limited to modulating aggregation behavior. Several lines of evidence point towards an inhibiting effect of asyn phosphorylation on membrane binding. For example, in both budding yeast and transgenic C. elegans, binding of asyn to plasma membranes is enhanced for the phosphorylation-deficient S129A mutation, while the phosphorylation mimicking S129D mutation results in decreased membrane binding. However, it is currently unknown how phosphorylation modulates membrane binding, i.e. whether it affects physiological monomer binding and/or membrane interactions of disease-associated asyn oligomers. The current study aimed at elucidating the influence of phosphorylation on interactions of asyn monomers and potentially toxic oligomers with model lipid membranes. Based on earlier findings from histopathological, epidemiological and experimental studies implicating an involvement of ferric iron in the pathogenesis of synucleinopathies, we have established a model of asyn oligomer formation yielding potentially toxic aggregates in presence of ferric iron.