Glucose metabolism in nerve terminals

- Neuronal activity upregulates glycolysis at nerve terminals.
- Glycolysis is essential for synaptic function.
- The availability of the cofactor NAD+ may be a limiting factor for glycolysis and ATP production in neurons.

Nerve terminals in the brain carry out the primary form of intercellular communication between neurons. Neurotransmission, however, requires adequate supply of ATP to support energetically demanding steps, including the maintenance of ionic gradients, reversing changes in intracellular Ca2+ that arise from opening voltage-gated Ca2+ channels, as well recycling synaptic vesicles. The energy demands of the brain are primarily met by glucose which is oxidized through glycolysis and oxidative phosphorylation to produce ATP. The pathways of ATP production have to respond rapidly to changes in energy demand at the synapse to sustain neuronal activity. In this review, we discuss recent progress in understanding the mechanisms regulating glycolysis at nerve terminals, their contribution to synaptic function, and how dysregulation of glycolysis may contribute to neurodegeneration.