Plasmonic nanoparticle amyloid corona for screening Aβ oligomeric aggregate-degrading drugs.

Dongtak Lee, Dongsung Park, Insu Kim, Sang Won Lee, Wonseok Lee, Kyo Seon Hwang, Jeong Hoon Lee, Gyudo Lee, Dae Sung Yoon

Nature communications 2021 Jan 27

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The generation of toxic amyloid β (Aβ) oligomers is a central feature of the onset and progression of Alzheimer's disease (AD). Drug discoveries for Aβ oligomer degradation have been hampered by the difficulty of Aβ oligomer purification and a lack of screening tools. Here, we report a plasmonic nanoparticle amyloid corona (PNAC) for quantifying the efficacy of Aβ oligomeric aggregate-degrading drugs. Our strategy is to monitor the drug-induced degradation of oligomeric aggregates by analyzing the colorimetric responses of PNACs. To test our strategy, we use Aβ-degrading proteases (protease XIV and MMP-9) and subsequently various small-molecule substances that have shown benefits in the treatment of AD. We demonstrate that this strategy with PNAC can identify effective drugs for eliminating oligomeric aggregates. Thus, this approach presents an appealing opportunity to reduce attrition problems in drug discovery for AD treatment.

Citation

Dongtak Lee, Dongsung Park, Insu Kim, Sang Won Lee, Wonseok Lee, Kyo Seon Hwang, Jeong Hoon Lee, Gyudo Lee, Dae Sung Yoon. Plasmonic nanoparticle amyloid corona for screening Aβ oligomeric aggregate-degrading drugs. Nature communications. 2021 Jan 27;12(1):639