The oxygen-sensing prolyl hydroxylase domain proteins (PHDs) regulate cellular metabolism, but their role in neuronal metabolism during stroke is unknown.

Researchers report that PHD1 deficiency provides neuroprotection in a murine model of permanent brain ischemia.

This was not due to an increased collateral vessel network. Instead, PHD1^−/− neurons were protected against oxygen-nutrient deprivation by reprogramming glucose metabolism.

Indeed, PHD1^−/−neurons enhanced glucose flux through the oxidative pentose phosphate pathway by diverting glucose away from glycolysis. As a result, PHD1^−/− neurons increased their redox buffering capacity to scavenge oxygen radicals in ischemia.

Intracerebroventricular injection of PHD1-antisense oligonucleotides reduced the cerebral infarct size and neurological deficits following stroke.

These data identify PHD1 as a regulator of neuronal metabolism and a potential therapeutic target in ischemic stroke.

http://www.cell.com/cell-metabolism/abstract/S1550-4131(15)00622-1