Flagmeier, P., De, S. orcid.org/0000-0003-1675-0773, Michaels, T.C.T. et al. (8 more authors) (2020) Direct measurement of lipid membrane disruption connects kinetics and toxicity of Aβ42 aggregation. Nature Structural & Molecular Biology, 27 (10). pp. 886-891. ISSN 1545-9993
Abstract
The formation of amyloid deposits in human tissues is a defining feature of more than 50 medical disorders, including Alzheimer’s disease. Strong genetic and histological evidence links these conditions to the process of protein aggregation, yet it has remained challenging to identify a definitive connection between aggregation and pathogenicity. Using time-resolved fluorescence microscopy of individual synthetic vesicles, we show for the Aβ42 peptide implicated in Alzheimer’s disease that the disruption of lipid bilayers correlates linearly with the time course of the levels of transient oligomers generated through secondary nucleation. These findings indicate a specific role of oligomers generated through the catalytic action of fibrillar species during the protein aggregation process in driving deleterious biological function and establish a direct causative connection between amyloid formation and its pathological effects.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 The Author(s). This is an author-produced version of a paper subsequently published in Nature Structural and Molecular Biology. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Neuroscience (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 11 Aug 2020 07:19 |
Last Modified: | 25 Jan 2022 09:02 |
Status: | Published |
Publisher: | Springer Nature |
Refereed: | Yes |
Identification Number: | 10.1038/s41594-020-0471-z |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:164281 |