被撤回的出版物: β-Amyloid and α-Synuclein Cooperate To Block SNARE-Dependent Vesicle Fusion(Retracted article. See vol. 56, pg.1026,2017)

Alzheimers disease (AD) and Parkinsons disease (PD) are caused by beta-amyloid (A beta) and a-synuclein (alpha S), respectively. Ample evidence suggests that these two pathogenic proteins are closely linked and have a synergistic effect on eliciting neurodegenerative disorders. However, the pathophysiological consequences of A beta and alpha S coexistence are still elusive. Here, we show that large-sized alpha S oligomers, which are normally difficult to form, are readily generated by A beta(42)-seeding and that these oligomers efficiently hamper neuronal SNARE-mediated vesicle fusion. The direct binding of the A beta-seeded alpha S oligomers to the N-terminal domain of synaptobrevin-2, a vesicular SNARE protein, is responsible for the inhibition of fusion. In contrast, large-sized A beta(42) oligomers (or aggregates) or the products of alpha S incubated without A beta(42) have no effect on vesicle fusion. These results are confirmed by examining PC12 cell exocytosis. Our results suggest that A beta and alpha S cooperate to escalate the production of toxic oligomers, whose main toxicity is the inhibition of vesicle fusion and consequently prompts synaptic dysfunction.