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Misfolded protein oligomers are of central importance in both the diagnosis and treatment of Alzheimer's and Parkinson's diseases. However, accurate high-throughput methods to detect and quantify oligomer populations are still needed. We present here a single-molecule approach for the detection and quantification of oligomeric species. The approach is based on the use of solid-state nanopores and multiplexed DNA barcoding to identify and characterize oligomers from multiple samples. We study α-synuclein oligomers in the presence of several small-molecule inhibitors of α-synuclein aggregation as an illustration of the potential applicability of this method to the development of diagnostic and therapeutic methods for Parkinson's disease.

Citation

Sarah E Sandler, Robert I Horne, Sara Rocchetti, Robert Novak, Nai-Shu Hsu, Marta Castellana Cruz, Z Faidon Brotzakis, Rebecca C Gregory, Sean Chia, Gonçalo J L Bernardes, Ulrich F Keyser, Michele Vendruscolo. Multiplexed Digital Characterization of Misfolded Protein Oligomers via Solid-State Nanopores. Journal of the American Chemical Society. 2023 Nov 29;145(47):25776-25788

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PMID: 37972287

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