Cavendish Laboratory, Maxwell Centre, Department of Physics, University of Cambridge, Cambridge CB3 0HE, U.K.
Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K.
J Am Chem Soc. 2023 Nov 29;145(47):25776-25788. doi: 10.1021/jacs.3c09335. Epub 2023 Nov 16.
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.
错误折叠的蛋白质寡聚体在阿尔茨海默病和帕金森病的诊断和治疗中都具有重要意义。然而，仍然需要准确的高通量方法来检测和定量寡聚体群体。我们在这里提出了一种用于检测和定量寡聚体的单分子方法。该方法基于使用固态纳米孔和多重 DNA 条形码来识别和表征来自多个样品的寡聚体。我们研究了α-突触核蛋白寡聚体在几种小分子抑制剂存在下的情况，这些抑制剂可以抑制α-突触核蛋白聚集，这说明了该方法在开发帕金森病的诊断和治疗方法方面的潜在适用性。
