Protein fibrous aggregation is associated with many neurodegenerative diseases including Alzheimer's and Parkinson's diseases. To modulate the process, a number of fibrillation inhibitors have been reported, although their working mechanism remains vague, calling for new means to decipher their interaction. Herein, we identified and characterized a novel inhibitor called Crocein Orange G (COG), which inhibited the nucleation and impeded the protofibril formation, revealed by various experimental approaches as well as molecular docking. In particular, the surface-enhanced Raman spectroscopy (SERS) helps to identify the binding sites and illustrate the interaction mechanism and fibrillation process by using Ag IMNPs as SERS substrate for a label-free detection. Combining with molecular docking, the SERS-based approach provides structural information concerning protein-ligand interaction and protein fibrillation. This study suggests that SERS can be a powerful new means to study the interaction between inhibitors and amyloid proteins and can potentially be a common tool for amyloid research. Strikingly, the SERS signal of COG corresponds very well with the state of protein fibrillation, hinting its function as an amyloid SERS signal amplifier. Therefore, this study provides a new means to monitor and interfere amyloid fibrillation.

蛋白质纤维聚集与许多神经退行性疾病有关，包括阿尔茨海默氏病和帕金森氏病。为了调节这一过程，已经报道了许多原纤化抑制剂，尽管它们的工作机制仍然模糊不清，要求采用新的手段来破译它们的相互作用。本文中，我们鉴定并表征了一种新型的抑制剂，称为克罗西丁橙G（COG），该抑制剂可抑制成核作用并阻止原纤维的形成，这是通过各种实验方法以及分子对接揭示的。特别是，表面增强拉曼光谱（SERS）通过使用Ag IMNPs作为SERS底物进行无标记检测，有助于鉴定结合位点并阐明相互作用机理和原纤化过程。结合分子对接 基于SERS的方法提供了有关蛋白-配体相互作用和蛋白原纤化的结构信息。这项研究表明，SERS可能是研究抑制剂与淀粉样蛋白之间相互作用的有力新手段，并且有可能成为淀粉样蛋白研究的常用工具。令人惊讶的是，COG的SERS信号与蛋白原纤化的状态非常吻合，暗示了其作为淀粉样蛋白SERS信号放大器的功能。因此，本研究提供了监测和干扰淀粉样蛋白原纤化的新手段。COG的SERS信号与蛋白原纤化的状态非常吻合，暗示其作为淀粉样蛋白SERS信号放大器的功能。因此，本研究提供了监测和干扰淀粉样蛋白原纤化的新手段。COG的SERS信号与蛋白原纤化的状态非常吻合，暗示其作为淀粉样蛋白SERS信号放大器的功能。因此，本研究提供了监测和干扰淀粉样蛋白原纤化的新手段。