Nanozyme scavenging ROS for prevention of pathologic α-synuclein transmission in Parkinson’s disease

Abstract 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 prion-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.