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

Braak's prion-like theory fundamentally subverts the understanding of Parkinson's disease (PD). Emerging evidence shows that pathologic alpha-synuclein (alpha-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, alpha-syn preformed fibrils (PFF) are used to model prion-like spreading and biocompatible antioxidant nanozyme, PtCu nanoalloys (NAs), is applied to fight against alpha-syn spreading. The results show that PtCu NAs significantly inhibit alpha-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 alpha-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. (C) 2020 Elsevier Ltd. All rights reserved.

Automated summary

Braak's prion-like theory challenges the conventional understanding of Parkinson's disease, while the use of nanomaterials like nanozyme to inhibit the spreading of alpha-synuclein shows potential as a therapeutic strategy against PD and other prion-like proteinopathies.