PRNP and Cerebral ischemia: Consistent with these findings, overexpression of PrPC was shown to provide a protective effect against focal cerebral ischemia via the activation of ERK, whereas downregulation of PrPC increased the exacerbation of ischemic brain injury through post-ischemic activation of caspase-3.41, 42 Moreover, PrPC was found to promote neuroprotection, neurogenesis, and angiogenesis in ischemic brain injuries.18