Amyloid formation of the synaptic brain proteinα-synuclein (αS) is related to degeneration of dopaminergic neurons in Parkinson's disease patients.αS is thought to function in vesicle transport and fusion and it binds strongly to negatively charged vesiclesin vitro. Here we combined circular dichroism, fluorescence and imaging methodsin vitroto characterize the interaction ofαS with negatively charged vesicles of DOPS (1,2-dioleoyl-sn-glycero-3-phospho-L-serine, sodium salt) and DOPG (1,2-dioleoyl-sn-glycero-3-phospho-(1′-rac-glycerol), sodium salt) and the consequences of such interactions onαS amyloid formation. We found that lipid head-group chemistry modulatesαS interactions and also affects amyloid fiber formation. During the course of the experiments, we made the unexpected discovery that pre-formedαS oligomers, typically present in a small amount in theαS starting material, acted as templates for linear growth of anomalous amyloid fibers in the presence of vesicles. At the same time, the remainingαS monomers were restricted from vesicle-mediated nucleation of amyloid fibers. Although not a dominant process in bulk experiments, this hiddenαS aggregation pathway may be of importancein vivo.

中文翻译：

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揭示阴离子囊泡引发的帕金森病蛋白 α-突触核蛋白的淀粉样蛋白形成途径

突触脑蛋白的淀粉样蛋白形成α-突触核蛋白（αS) 与帕金森病患者多巴胺能神经元的退化有关。αS被认为在囊泡运输和融合中起作用，它与带负电荷的囊泡强烈结合体外. 在这里，我们结合了圆二色性、荧光和成像方法体外来表征相互作用的αS 带有带负电荷的 DOPS 囊泡（1,2-二油酰-sn-glycero-3-phospho-L-serine, sodium salt) 和 DOPG (1,2-dioleoyl-sn-甘油-3-磷酸-(1'-拉克-甘油），钠盐）和这种相互作用的后果αS淀粉样蛋白的形成。我们发现脂质头基化学调节αS 相互作用，也影响淀粉样纤维的形成。在实验过程中，我们意外地发现了预先形成的αS 低聚物，通常以少量存在于αS 起始材料，用作在存在囊泡的情况下异常淀粉样纤维线性生长的模板。同时，剩余的αS 单体受到囊泡介导的淀粉样蛋白纤维成核的限制。虽然不是批量实验中的主要过程，但这种隐藏的αS 聚集途径可能很重要体内.