Partner: G. Spencer Nicholas


Ostatnie publikacje
1.Daniels Michael J.D., Rivers-Auty J., Schilling T., Spencer Nicholas G., Watremez W., Fasolino V., Booth Sophie J., White Claire S., Baldwin Alex G., Freeman S., Wong R., Latta C., Yu S., Jackson J., Fischer N., Koziel V., Pillot T., Bagnall J., Allan Stuart M., Paszek P., Galea J., Harte Michael K., Eder C., Lawrence Catherine B., Brough D., Fenamate NSAIDs inhibit the NLRP3 inflammasome and protect against Alzheimer’s disease in rodent models, Nature Communications, ISSN: 2041-1723, DOI: 10.1038/ncomms12504, Vol.7, pp.12504-1-10, 2016

Streszczenie:

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.

Afiliacje autorów:

Daniels Michael J.D.-other affiliation
Rivers-Auty J.-other affiliation
Schilling T.-other affiliation
Spencer Nicholas G.-other affiliation
Watremez W.-other affiliation
Fasolino V.-other affiliation
Booth Sophie J.-other affiliation
White Claire S.-other affiliation
Baldwin Alex G.-other affiliation
Freeman S.-other affiliation
Wong R.-other affiliation
Latta C.-other affiliation
Yu S.-other affiliation
Jackson J.-other affiliation
Fischer N.-other affiliation
Koziel V.-other affiliation
Pillot T.-other affiliation
Bagnall J.-other affiliation
Allan Stuart M.-other affiliation
Paszek P.-other affiliation
Galea J.-other affiliation
Harte Michael K.-other affiliation
Eder C.-other affiliation
Lawrence Catherine B.-other affiliation
Brough D.-other affiliation
45p.