Properties of native brain α-synuclein

α-Synuclein is an abundant presynaptic protein that binds to negatively charged phospholipids, functions as a SNARE-complex chaperone and contributes to Parkinson's disease pathogenesis. Recombinant α-synuclein in solution is largely unfolded and devoid of tertiary structure, but Bartels et al. have proposed that native α-synuclein purified from human erythrocytes forms a stably folded, soluble tetramer that resists aggregation. By contrast, we show here that native α-synuclein purified from mouse brain consists of a largely unstructured monomer, exhibits no stable tetramer formation, and is prone to aggregation. The native state of α-synuclein is important for understanding its pathological effects as a stably folded protein would be much less prone to aggregation than a conformationally labile protein. There is a Reply to this Brief Communication Arising by Bartels. © 2013 Macmillan Publishers Limited. All rights reserved.