PRNP and brain ischemia: We have previously shown that overexpression of PrPc results reduces phosphorylation of ERK-1/2 after focal cerebral ischemia in mice.23 ERK-1/2 is activated by the proteasome,26, 27, 28 which aggravates post-ischemic brain injury via increased oxidative stress and hypoxia-inducible factor 1α (HIF-1α) degradation.29 To elucidate the role of proteasome activation in PrPc-induced neuroprotection, we measured proteasomal activity 24 h after 45 min of MCA occlusion.