Multiplexed Digital Characterization of Misfolded Protein Oligomers via Solid-State Nanopores.

Autor: Sandler SE; Cavendish Laboratory, Maxwell Centre, Department of Physics, University of Cambridge, Cambridge CB3 0HE, U.K., Horne RI; Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K., Rocchetti S; Cavendish Laboratory, Maxwell Centre, Department of Physics, University of Cambridge, Cambridge CB3 0HE, U.K., Novak R; Cavendish Laboratory, Maxwell Centre, Department of Physics, University of Cambridge, Cambridge CB3 0HE, U.K., Hsu NS; Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K., Castellana Cruz M; Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K., Faidon Brotzakis Z; Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K., Gregory RC; Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K., Chia S; Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K.; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), Singapore 138668., Bernardes GJL; Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K., Keyser UF; Cavendish Laboratory, Maxwell Centre, Department of Physics, University of Cambridge, Cambridge CB3 0HE, U.K., Vendruscolo M; Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K.
Jazyk: angličtina
Zdroj: Journal of the American Chemical Society [J Am Chem Soc] 2023 Nov 29; Vol. 145 (47), pp. 25776-25788. Date of Electronic Publication: 2023 Nov 16.
DOI: 10.1021/jacs.3c09335
Abstrakt: 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.
Databáze: MEDLINE