Reevaluating Metabolism in Alzheimer's Disease from the Perspective of the Astrocyte-Neuron Lactate Shuttle Model

Figure 1

The astrocyte-neuron lactate shuttle hypothesis. The activation of nerve cells leads to the release of the neurotransmitter glutamate. Glutamate is actively taken up into astrocytes by glutamate transporters (GLT-1) and is converted into glutamine. The uptake of glutamate into astrocytes stimulates both increased glucose uptake from surrounding capillaries via glucose transporters (GLUT1) and increased aerobic glycolysis. Aerobic glycolysis can also be stimulated by the breakdown of intracellular stores of glycogen. Pyruvate is converted to lactate by lactate dehydrogenase isoenzyme A (LDHA) and is exported out of the cell by the monocarboxylate transporter 1 or 4 (MCT1/4) and transported into nerve cells via MCT2. LDHB within nerve cells coverts lactate to pyruvate which is used to fuel oxidative phosphorylation within mitochondria. Glucose can also enter nerve cells via GLUT3 transporters.