Figure 2. The WNT pathway and glutamate in AD. Under physiological conditions, glutamate released from the presynaptic neuron stimulates ionotropic glutamate receptors present on the postsynaptic neuron. The resulting influx of Na+ and Ca2+ into the cell leads to depolarization and generation of an action potential. However, chronic elevation of glutamate through impairment of EAAT2 and GS causes neuronal damage and leads to AD. In AD, the downregulation of β-catenin signaling inhibits the activity of EAAT2. Chronic accumulation of glutamate (through an impaired EAAT2 function, as glutamate reuptake function) induces excitotoxicity and then, neuronal death.