HK1 and brain ischemia: Under cerebral ischemia, the neurons upregulate hexokinase (HK), phosphofructokinase 1 (PFK1), pyruvate kinase M1 (PKM1), and lactate dehydrogenase (LDH) through HIF-1α/mTORC1 signaling, driving global glycolytic flux amplification to rapidly generate ATP and regenerate NAD+ for sustaining anaerobic glycolysis [29].