Braak’s prion-like theory fundamentally subverts the understanding of Parkinson’s disease (PD). Emerging evidence shows that pathologic α-synuclein (α-syn) is a -like protein that spreads from one region to another in PD brain, which is an essential driver to the pathogenesis of PD. Thus far, there is a big knowledge gap that limited nanomaterial that can block prion-like spreading. Here, α-syn preformed fibrils (PFF) are used to model prion-like spreading and biocompatible antioxidant nanozyme, PtCu nanoalloys (NAs), is applied to fight against α-syn spreading. The results show that PtCu NAs significantly inhibit α-syn pathology, cell death, and neuron-to-neuron transmission by scavenging reactive oxygen species (ROS) in primary neuron cultures. Moreover, the PtCu NAs significantly inhibit α-syn spreading induced by intrastriatal injection of PFF. It is the first time to observe nanozyme can block prion-like spreading, which provides a proof of concept for nanozyme therapy. It is also anticipated that the biomedical application of nanozyme against prion-like spreading could be optimized and considered to be developed as a therapeutic strategy against Parkinson’s disease, Alzheimer’s disease, and other prion-like proteinopathies.

中文翻译：

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纳米酶清除 ROS 预防帕金森病病理性 α-突触核蛋白传播

布拉克的类朊病毒理论从根本上颠覆了人们对帕金森病（PD）的认识。新的证据表明，病理性 α-突触核蛋白 (α-syn) 是一种类似蛋白质，在 PD 大脑中从一个区域扩散到另一个区域，是 PD 发病机制的重要驱动因素。到目前为止，对于阻止朊病毒传播的纳米材料还存在很大的知识空白。在这里，α-syn 预制原纤维 (PFF) 用于模拟朊病毒样扩散，生物相容性抗氧化剂纳米酶、PtCu 纳米合金 (NAs) 用于对抗 α-syn 扩散。结果表明，PtCu NA 通过清除原代神经元培养物中的活性氧 (ROS)，显着抑制 α-syn 病理、细胞死亡和神经元间传递。此外，PtCu NAs 显着抑制纹状体内注射 PFF 诱导的 α-syn 扩散。这是首次观察到纳米酶可以阻止朊病毒样传播，这为纳米酶治疗提供了概念证明。还预计纳米酶对抗朊病毒样扩散的生物医学应用可以得到优化，并被考虑开发为针对帕金森病、阿尔茨海默病和其他朊病毒样蛋白病的治疗策略。