Inhibiting the NLRP3 inflammasome with MCC950 promotes non-phlogistic clearance of amyloid-β and cognitive function in APP/PS1 mice

• Published in: Brain, behavior, and immunity Vol. 61; pp. 306 - 316
• Main Authors: Dempsey, C, Rubio Araiz, A, Bryson, K.J, Finucane, O, Larkin, C, Mills, E.L, Robertson, A.A.B, Cooper, M.A, O'Neill, L.A.J, Lynch, M.A
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.03.2017
• Subjects: Allergy and Immunology; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer’s disease; Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - genetics; Amyloid beta-Protein Precursor - metabolism; Animals; APP/PS1 mice; Caspase 1; Cognition - drug effects; Disease Models, Animal; Heterocyclic Compounds, 4 or More Rings - pharmacology; Inflammasome; Inflammasomes - drug effects; Inflammasomes - metabolism; Interleukin-1β; Mice; Microglia; Microglia - drug effects; Microglia - metabolism; Neuroinflammation; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Presenilin-1 - genetics; Presenilin-1 - metabolism; Psychiatry; Sulfones - pharmacology; APP/PS1 mice; Interleukin-1β; Neuroinflammation; Caspase 1; Inflammasome; Alzheimer's disease; Microglia; Alzheimer’s disease
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2016.12.014

Highlights • The small molecule inhibitor of the inflammasome, MC950, attenuates Aβ+LPS-induced inflammasome activation in microglia. • It increases phagocytosis of Aβ by microglia in vitro. • Oral administration of MC950, reduces Aβ accumulation in APP/PS1 mice. • This is accompanied by improved cognitive function and decreased neuroinflammation.