Cawood, EE, Karamanos, TK orcid.org/0000-0003-2297-540X, Wilson, AJ orcid.org/0000-0001-9852-6366 et al. (1 more author) (2021) Visualizing and trapping transient oligomers in amyloid assembly pathways. Biophysical Chemistry, 268. 106505. ISSN 0301-4622
Abstract
Oligomers which form during amyloid fibril assembly are considered to be key contributors towards amyloid disease. However, understanding how such intermediates form, their structure, and mechanisms of toxicity presents significant challenges due to their transient and heterogeneous nature. Here, we discuss two different strategies for addressing these challenges: use of (1) methods capable of detecting lowly-populated species within complex mixtures, such as NMR, single particle methods (including fluorescence and force spectroscopy), and mass spectrometry; and (2) chemical and biological tools to bias the amyloid energy landscape towards specific oligomeric states. While the former methods are well suited to following the kinetics of amyloid assembly and obtaining low-resolution structural information, the latter are capable of producing oligomer samples for high-resolution structural studies and inferring structure-toxicity relationships. Together, these different approaches should enable a clearer picture to be gained of the nature and role of oligomeric intermediates in amyloid formation and disease.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
Keywords: | Amyloid disease; Transient intermediate; Oligomer stabilization; Chemical tool; NMR; Single particle |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemistry (Leeds) > Organic Chemistry (Leeds) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Structural Molecular Biology (Leeds) |
Funding Information: | Funder Grant number Wellcome Trust 109154/Z/15/Z Wellcome Trust 204963/Z/16/Z EPSRC (Engineering and Physical Sciences Research Council) EP/N035267/1 EU - European Union 322408 |
Depositing User: | Symplectic Publications |
Date Deposited: | 05 Nov 2020 10:17 |
Last Modified: | 31 Mar 2022 15:09 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.bpc.2020.106505 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:167554 |