Ganglioside lipids accelerate α-synuclein amyloid formation
Ganglioside lipids accelerate α-synuclein amyloid formation
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DOI：
10.1016/j.bbapap.2018.07.004
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发表时间：
2018-10-01
影响因子：
3.2
通讯作者：
Sparr, Emma
中科院分区：
文献类型：
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作者：
Gaspar, Ricardo;Pallbo, Jon;Sparr, Emma
α-突触核蛋白纤维的沉积是帕金森氏症的一个特征。在这里，我们研究神经节苷脂是如何影响α-突触核蛋白的聚集动力学的，神经节苷脂在神经元和外体中含量很高。神经节苷脂以及其他具有小或大头基的阴离子脂质物种在中等酸性条件下可以诱导α-突触核蛋白单体的构象变化并催化它们的聚集。尽管神经节苷脂的这种催化作用的程度略高，但结果表明，在触发聚集方面，电荷相互作用比头基化学更重要。支持这一观点的是，含有大头基的不带电荷的脂类没有引起任何构象变化，只能微弱地催化聚集。有趣的是，神经节苷脂游离基也触发了聚集，而这些并没有引起α-突触核蛋白单体的构象变化。我们的数据表明，部分折叠的α-突触核蛋白螺旋中间体不是触发α-突触核蛋白聚集的必需物种。
The deposition of alpha-synuclein fibrils is one hallmark of Parkinson's disease. Here, we investigate how ganglioside lipids, present in high amounts in neurons and exosomes, influence the aggregation kinetics of alpha-synuclein. Gangliosides, as well as, other anionic lipid species with small or large headgroups were found to induce conformational changes of alpha-synuclein monomers and catalyse their aggregation at mildly acidic conditions. Although the extent of this catalytic effect was slightly higher for gangliosides, the results imply that charge interactions are more important than headgroup chemistry in triggering aggregation. In support of this idea, uncharged lipids with large headgroups were not found to induce any conformational change and only weakly catalyse aggregation. Intriguingly, aggregation was also triggered by free ganglioside headgroups, while these caused no conformational change of alpha-synuclein monomers. Our data reveal that partially folded alpha-synuclein helical intermediates are not required species in triggering of alpha-synuclein aggregation.