Glia and neurons in the brain can respond differently to stressful conditions. For example, glia survive when exposed to levels of nitric oxide (NO) that are toxic to neurons. Almeida et al. examined this difference in sensitivity in cultured cells and report that the difference in expression of a single enzyme may be responsible. NO exposure is known to inhibit cellular respiration, and this appears to trigger an increase in glycolysis in astrocytes, which enables them to maintain energy production. Neurons cannot engage in this process because they do not express a specific isoform of the enzyme 6-phosphofructo-2-kinase (PFK2). PFK2 generates fructose-2,6-bisphosphate, an allosteric activator of the enzyme PFK1. Activation of PFK1 enhances glycolysis and is neuroprotective. Moreover, activation of PFK2 was linked to adenosine monophosphate-activated protein kinase, an enzyme that is stimulated during respiratory inhibition. The presence or absence of a single isoform of PFK2 in astrocytes and neurons, respectively, illustrates how subtle differences may determine a neurotoxic or neuroprotective response to cell stressors.
A. Almeida, S. Moncada, J. P. Bolaños, Nitric oxide switched on glycolysis through the AMP protein kinase and 6-phosphofructo-2-kinase pathway. Nat. Cell Biol. 6, 45-51 (2004). [Online Journal]