α-Synuclein Can Function as an Antioxidant Preventing Oxidation of Unsaturated Lipid in Vesicles

Abstract

α-Synuclein, a presynaptic protein associated with Parkinson's disease, is found as both soluble cytosolic and membrane-bound forms. Although the function of α-synuclein is unknown, several observations suggest that its association with membranes is important. In the present study we investigated the effect of α-synuclein on lipid oxidation in membranes containing phospholipids with unsaturated fatty acids. The kinetics of lipid oxidation were monitored by the change in fluorescence intensity of the dye C11-BODIPY. We find that monomeric α-synuclein efficiently prevented lipid oxidation, whereas fibrillar α-synuclein had no such effect. Our data suggest that the prevention of unsaturated lipid oxidation by α-synuclein requires that it bind to the lipid membrane. The antioxidant function of α-synuclein is attributed to its facile oxidation via the formation of methionine sulfoxide, as shown by mass spectrometry. These findings suggest that the inhibition of lipid oxidation by α-synuclein may be a physiological function of the protein.