Human full-length (fl) αSyn fibrils, key neuropathological hallmarks of Parkinson's disease (PD), generate intense optical activity corresponding to the surface plasmon resonance of interacting gold nanorods. Herein, we analysed fibril-enriched protein extracts from mouse and human brain samples as well as from SK-N-SH cell lines with or without human fl and C-terminally truncated (Ctt) αSyn overexpression and exposed them to αSyn monomers, recombinant fl αSyn fibrils or Ctt αSyn fibrils. In vitro-generated human recombinant fl and Ctt αSyn fibrils and fibrils purified from SK-N-SH cells with fl or Ctt αSyn overexpression were also analysed using transmission electron microscopy (TEM) to gain insights into the nanorod-fibril complexes. We found that under the same experimental conditions, bisignate circular dichroism (CD) spectra of Ctt αSyn fibrils exhibited a blue-wavelength shift compared to that of fl αSyn fibrils. TEM results supported that this could be attributed to the different properties of nanorods. In our experimental conditions, fibril-enriched PD brain extract broadened the longitudinal surface plasmonic band with a bisignate CD couplet centred corresponding to the absorption band maximum. Plasmonic CD (PCD) couplets of in vivo- and in vitro-generated fibrils displayed sign reversal, suggesting their opposite handedness. Moreover, the incubation of in vitro-generated human recombinant fl αSyn fibrils in mouse brain extracts from αSyn null mice resulted in PCD couplet inversion, indicating that the biological environment may shape the handedness of αSyn fibrils. These findings support that nanorod-based PCD can provide useful information on the composition and features of αSyn fibrils from biological materials.

中文翻译：

---

纳米棒相关等离子体圆二色谱性监测帕金森病模型和死后脑中 α-突触核蛋白原纤维的旋性和组成


人类全长 （fl） αSyn 原纤维是帕金森病 （PD） 的关键神经病理学标志，可产生与相互作用的金纳米棒的表面等离子体共振相对应的强烈光学活性。在此，我们分析了来自小鼠和人脑样品以及具有或不具有人 fl 和 C 末端截短 （Ctt） αSyn 过表达的 SK-N-SH 细胞系的富含原纤维的蛋白质提取物，并将它们暴露于 αSyn 单体、重组 fl αSyn 原纤维或 Ctt αSyn 原纤维。体外生成的人重组 fl 和 Ctt αSyn 原纤维以及从具有 fl 或 Ctt αSyn 过表达的 SK-N-SH 细胞中纯化的原纤维也使用透射电子显微镜 （TEM） 进行分析，以深入了解纳米棒-原纤维复合物。我们发现，在相同的实验条件下，Ctt αSyn 原纤维的双signate 圆二色谱 （CD） 光谱与 fl αSyn 原纤维相比表现出蓝色波长偏移。TEM 结果支持这可能是由于纳米棒的不同性质。在我们的实验条件下，富含原纤维的 PD 脑提取物拓宽了纵向表面等离子体带，其中心是对应于吸收带最大值的双基 CD 对。体内和体外产生的原纤维的等离子体 CD （PCD） 对联显示符号反转，表明它们的旋向相反。此外，在 αSyn 无效小鼠的小鼠脑提取物中体外生成的人重组 fl αSyn 原纤维的孵育导致 PCD 对位，表明生物环境可能塑造 αSyn 原纤维的旋性。这些发现支持基于纳米棒的 PCD 可以提供有关生物材料中 αSyn 原纤维的组成和特征的有用信息。