Whiten, D.R., Brownjohn, P.W., Moore, S. et al. (6 more authors) (2020) TNF induces increased production of extracellular amyloid-β- and α-synuclein-containing aggregates by human Alzheimer’s disease neurons. Brain Communications, 2 (2). fcaa146. ISSN 2632-1297
Abstract
In addition to increased aberrant protein aggregation, inflammation has been proposed as a key element in the pathogenesis and progression of Alzheimer’s disease. How inflammation interacts with other disease pathways and how protein aggregation increases during disease are not clear. We used single molecule imaging approaches and membrane permeabilisation assays to determine the effect of chronic exposure to TNF, a master proinflammatory cytokine, on protein aggregation in human induced pluripotent stem cell-derived neurons harbouring monogenic Alzheimer’s disease mutations. We report that exposure of Alzheimer’s disease, but not control, neurons to TNF induces substantial production of extracellular protein aggregates. Aggregates from Alzheimer’s disease neurons are composed of amyloid-β and α-synuclein and induce significant permeabilisation of lipid membranes in an assay of pathogenicity. These findings provide support for a causal relationship between two crucial processes in Alzheimer’s disease pathogenesis, and suggest that targeting inflammation, particularly TNF, may have beneficial downstream effects on ameliorating aberrant protein aggregation and accumulation.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
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: | 06 Oct 2020 11:32 |
Last Modified: | 26 Jan 2022 16:46 |
Status: | Published |
Publisher: | Oxford University Press (OUP) |
Refereed: | Yes |
Identification Number: | 10.1093/braincomms/fcaa146 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:165832 |