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

ABSTRACT: The generation of toxic amyloid ? (A?) oligomers is a central feature of the onset and progression of Alzheimer's disease (AD). Drug discoveries for A? oligomer degradation have been hampered by the difficulty of A? oligomer purification and a lack of screening tools. Here, we report a plasmonic nanoparticle amyloid corona (PNAC) for quantifying the efficacy of A? 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 A?-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.

SUBMITTER: Lee D 

PROVIDER: S-EPMC7840768 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature