Daniels, MJD;
Rivers-Auty, J;
Schilling, T;
Spencer, NG;
Watremez, W;
Fasolino, V;
Booth, SJ;
White, CS;
Baldwin, AG;
Freeman, S;
et al.
Daniels, MJD; Rivers-Auty, J; Schilling, T; Spencer, NG; Watremez, W; Fasolino, V; Booth, SJ; White, CS; Baldwin, AG; Freeman, S; Wong, R; Latta, C; Yu, S; Jackson, J; Fischer, N; Koziel, V; Pillot, T; Bagnall, J; Allan, SM; Paszek, P; Galea, J; Harte, MK; Eder, C; Lawrence, CB; Brough, D
(2016)
Fenamate NSAIDs inhibit the NLRP3 inflammasome and protect against Alzheimer's disease in rodent models.
Nature Commununications, 7.
p. 12504.
ISSN 2041-1723
https://doi.org/10.1038/ncomms12504
SGUL Authors: Eder, Claudia Schilling, Tom
Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase-1 (COX-1) and COX-2 enzymes. The NLRP3 inflammasome is a multi-protein complex responsible for the processing of the proinflammatory cytokine interleukin-1β and is implicated in many inflammatory diseases. Here we show that several clinically approved and widely used NSAIDs of the fenamate class are effective and selective inhibitors of the NLRP3 inflammasome via inhibition of the volume-regulated anion channel in macrophages, independently of COX enzymes. Flufenamic acid and mefenamic acid are efficacious in NLRP3-dependent rodent models of inflammation in air pouch and peritoneum. We also show therapeutic effects of fenamates using a model of amyloid beta induced memory loss and a transgenic mouse model of Alzheimer's disease. These data suggest that fenamate NSAIDs could be repurposed as NLRP3 inflammasome inhibitors and Alzheimer's disease therapeutics.
| Item Type: |
Article
|
| Additional Information: |
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: |
MD Multidisciplinary |
| SGUL Research Institute / Research Centre: |
Academic Structure > Infection and Immunity Research Institute (INII) |
| Journal or Publication Title: |
Nature Commununications |
| Article Number: |
12504 (2016) |
| ISSN: |
2041-1723 |
| Language: |
eng |
| Dates: |
| Date | Event |
|---|
| 11 August 2016 | Published Online | | 6 July 2016 | Accepted |
|
| Publisher License: |
Creative Commons: Attribution 4.0 |
| Projects: |
|
| PubMed ID: |
27509875 |
 |
Go to PubMed abstract |
| URI: |
https://openaccess.sgul.ac.uk/id/eprint/108276 |
| Publisher's version: |
https://doi.org/10.1038/ncomms12504 |
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