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

J Am Chem Soc. 2023 Nov 29;145(47):25776-25788. doi: 10.1021/jacs.3c09335. Epub 2023 Nov 16.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Nanopores*
  • Parkinson Disease* / metabolism
  • alpha-Synuclein / metabolism

Substances

  • alpha-Synuclein