The assembly of α-synuclein (αS) oligomers is recognized as the main pathological driver of synucleinopathies. While the elimination of toxic αS oligomers shows promise for the treatment of Parkinson's disease (PD), the discovery of αS oligomer degradation drugs has been hindered by the lack of proper drug screening tools. Here, we report a drug screening platform for monitoring the efficacy of αS-oligomer-degrading drugs using amyloid-shelled gold nanocomplexes (ASGNs). We fabricate ASGNs in the presence of dopamine, mimicking the in vivo generation process of pathological αS oligomers. To test our platform, the first of its kind for PD drugs, we use αS-degrading proteases and various small molecular substances that have shown efficacy in PD treatment. We demonstrate that the ASGN-based in vitro platform has strong potential to discover effective αS-oligomer-targeting drugs, and thus it may reduce the attrition problem in drug discovery for PD treatment.
Bibliographical noteFunding Information:
This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean Government (MSIP) (nos. NRF-2018M3C1B7020722, NRF-2020R1A2C2102262, NRF-2022R1A6A3A13072828, NRF-2022R1A2C1091756 and NRF-2022R1A6A3A03066467), BK21 Four Institute of Precision Public Health, and the Korea University Graduate School Junior Fellow Research Grant. This work was also supported by the Bio & Medical Technology Development Program of the NRF funded by the Korean government (MSIT) (no. 2021M3E5E3080743) and Korea Health Industry Development Institute (KHIDI) grant HU21C0053.
- Parkinson's disease
- amyloid corona
- drug screening
- plasmonic nanoparticle
ASJC Scopus subject areas
- Materials Science(all)