Inhibiting NLRP3 Inflammasome Activation by CY-09 Helps to Restore Cerebral Glucose Metabolism in 3×Tg-AD Mice

The decrease in the cerebral glucose metabolic process is carefully associated with the activation from the NOD-like receptor protein 3 (NLRP3) inflammasome in Alzheimer’s (AD) however, its underlying mechanism remains unclear. Within this paper, 18F-flurodeoxyglucose positron emission tomography was utilized to follow cerebral glucose metabolic process in vivo, together with Western blotting and immunofluorescence assays to look at the expression and distribution of connected proteins. Glucose and insulin tolerance tests were transported to identify insulin resistance, and also the Morris water maze was utilized to check the spatial learning and memory ability from the rodents. The outcomes show elevated NLRP3 inflammasome activation, elevated insulin resistance, and decreased glucose metabolic process in 3×Tg-AD rodents. Inhibiting NLRP3 inflammasome activation using CY-09, a particular inhibitor for NLRP3, may restore cerebral glucose metabolic process by growing the expression and distribution of glucose transporters and enzymes and attenuating insulin resistance in AD rodents. Furthermore, CY-09 helps you to improve AD pathology as well as reducing cognitive impairment during these rodents. Although CY-09 doesn’t have important effect on ferroptosis, it may effectively reduce essential fatty acid synthesis and fat peroxidation. These bits of information provide new evidence for NLRP3 inflammasome like a therapeutic target for AD, suggesting that CY-09 can be a potential drug to treat this ailment.