ThX – A next-generation probe for the early detection of amyloid aggregates
| Autor: | Judith Weber, Thomas N. Snaddon, Rachel Cliffe, Benjamin Keenlyside, Lisa-Maria Needham, Sarah E. Bohndiek, David Klenerman, Steven F. Lee, Christopher M. Dobson, Dung T. Do, Christopher A. Hunter, Juan A. Varela, James W. B. Fyfe, Catherine K. Xu |
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| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
Amyloid Binding properties Early detection 010402 general chemistry 01 natural sciences Fluorescence 0104 chemical sciences Amyloidogenic Proteins 03 medical and health sciences chemistry.chemical_compound chemistry Biophysics Thioflavin Protein folding Cytotoxicity 030304 developmental biology |
| Popis: | 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, we demonstrate that ThX can be used to detect a distinct oligomeric species, not observed via traditional ThT imaging. |
| Databáze: | OpenAIRE |
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