In ACS applied materials & interfaces ; h5-index 147.0
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.
Lee Dongtak, Jung Hyo Gi, Park Dongsung, Bang Junho, Hong Ji Hye, Lee Sang Won, Roh Seokbeom, Jang Jae Won, Kim Yonghwan, Hwang Kyo Seon, Lee Young-Sun, Park Jae-Yong, Jung In Duk, Lee Jeong Hoon, Lee Gyudo, Yoon Dae Sung
2022-Dec-22
Parkinson’s disease, amyloid corona, drug screening, plasmonic nanoparticle, α-synuclein
