Cellular Prion Protein (PrP c ) and Hypoxia: True to Each Other in Good Times and in Bad, in Sickness, and in Health.

The cellular prion protein (PrP ^c ) and hypoxia appear to be tightly intertwined. Beneficial effects of PrP ^c on neuronal survival under hypoxic conditions such as focal cerebral ischemia are strongly supported. Conversely, increasing evidence indicates detrimental effects of increased PrP ^c expression on cancer progression, another condition accompanied by low oxygen tensions. A switch between anaerobic and aerobic metabolism characterizes both conditions. A cellular process that might unite both is glycolysis. Putative role of PrP ^c in stimulation of glycolysis in times of need is indeed thought provoking. A significance of astrocytic PrP ^c expression for neuronal survival under hypoxic conditions and possible association of PrP ^c with the astrocyte-neuron lactate shuttle is considered. We posit PrP ^c -induced lactate production via transactivation of lactate dehydrogenase A by hypoxia inducible factor 1α as an important factor for survival of both neurons and tumor cells in hypoxic microenvironment. Concomitantly, we discuss a cross-talk between Wnt/β-catenin and PI3K/Akt signaling pathways in executing PrP ^c -induced activation of glycolysis. Finally, we would like to emphasize that we see a great potential in joining expertise from both fields, neuroscience and cancer research in revealing the mechanisms underlying hypoxia-related pathologies. PrP ^c may prove focal point for future research.