Brain energy metabolism in glutamate-receptor activation and excitotoxicity: Role for APC/C-Cdh1 in the balance glycolysis/pentose phosphate pathway

► Current concepts in brain energy metabolism and excitotoxic mechanisms are reviewed. ► Glutamate neurotransmission is coupled with changes in glucose metabolism. ► APC/C-Cdh1 targets PFKFB3 for degradation and inhibits glycolysis in neurons. ► NMDAR activation inhibits APC/C-Cdh1 and stabilizes PFKFB3 increasing glycolysis. ► PFKFB3 stabilization inhibits pentose-phosphate pathway and causes oxidative stress.