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ThX – a next-generation probe for the early detection of amyloid aggregates

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Abstract

Neurodegenerative diseases such as Alzheimer's and Parkinson's are associated with protein misfolding and aggregation. Recent studies suggest that the small, rare and heterogeneous oligomeric species, formed early on in the aggregation process, may be a source of cytotoxicity. Thioflavin T (ThT) is currently the gold-standard fluorescent probe for the study of amyloid proteins and aggregation processes. However, the poor photophysical and binding properties of ThT impairs the study of oligomers. To overcome this challenge, we have designed Thioflavin X, (ThX), a next-generation fluorescent probe which displays superior properties; including a 5-fold increase in brightness and 7-fold increase in binding affinity to amyloidogenic proteins. As an extrinsic dye, this can be used to study unique structural amyloid features both in bulk and on a single-aggregate level. Furthermore, ThX can be used as a super-resolution imaging probe in single-molecule localisation microscopy. Finally, the improved optical properties (extinction coefficient, quantum yield and brightness) of ThX can be used to monitor structural differences in oligomeric species, not observed via traditional ThT imaging.

Graphical abstract: ThX – a next-generation probe for the early detection of amyloid aggregates

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Supplementary files

Article information


Submitted
19 Sep 2019
Accepted
27 Jan 2020
First published
21 Feb 2020

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2020, Advance Article
Article type
Edge Article

ThX – a next-generation probe for the early detection of amyloid aggregates

L. Needham, J. Weber, J. A. Varela, J. W. B. Fyfe, D. T. Do, C. K. Xu, L. Tutton, R. Cliffe, B. Keenlyside, D. Klenerman, C. M. Dobson, C. A. Hunter, K. H. Müller, K. O'Holleran, S. E. Bohndiek, T. N. Snaddon and S. F. Lee, Chem. Sci., 2020, Advance Article , DOI: 10.1039/C9SC04730A

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