Metabolic Switch Targeting for A1→A2 Repolarization

**Molecular Mechanism and Rationale** The hexokinase 2 (HK2)-mediated metabolic switch represents a fundamental regulatory mechanism governing astrocyte phenotypic polarization between the neurotoxic A1 and neuroprotective A2 states. HK2, the predominant hexokinase isoform in the brain, catalyzes the ATP-dependent phosphorylation of glucose to glucose-6-phosphate, the rate-limiting step of glycolysis. This enzyme's unique mitochondrial localization through its interaction with the voltage-depen...