If neurons use glucose for oxidative stress defense, then where do get the energy? Astrocytes, close neighboring neurons and cerebral microvessels, metabolize glucose very quickly that catch the blood. To this end, dependent protein kinase 5′-AMP (AMPK) is responsible to keep active Pfkfb3 providing a robust glycolytic activity. Moreover, removal of glutamate from the synaptic cleft, astrocytes engaged to enable neurotransmission, is coupled, through a bioenergetic mechanism-a activation of glycolysis.

1 This forces restore NAD + / NADH (H + ) by conversion of pyruvate to lactate, which is released into the extracellular medium, from which is taken up by neurons and convert it into pyruvate and used as energy source in mitochondria. Thus, glycolytic metabolism of astrocytes preferably cooperates with neurons allowing glucose to intended purposes and protecting antioxidants apoptosis. 2 In addition, this mechanism could also be very relevant in cancer, where it operates a similar mechanism of metabolic regulation.

It remains to know if the way CDH1-Pfkfb3 described is subject to physiological regulation in vivo. It is known that CDH1, known for its role in genome stability and tumor suppression, is inhibited by phosphorylation in neurons during glutamatergic stimulation. 3 neurotransmission may be coupled through CDH1, the regulation of neuronal glycolysis through mechanisms that require further investigation. Given the importance of carbohydrate metabolism has on neuronal survival, knowledge of these mechanisms could help to establish new molecular targets to take into account neurological disorders.