In Vivo Neuroprotective Properties and Action Mechanism(s) of Plant-produced Asialo-erythropoietin

Abstract
There is an acute need to develop neuroprotective drugs to prevent or/and protect neuronal cell
damage and death caused by ischemia/reperfusion, hypoxia or cytotoxic agents in the brain. Plant-
based expression system can be used to produce asialo-rhuEPO, a non-hematopoietic
recombinant human EPO derivative lacking sialic acid, which could be used as a neuroprotective
agent for preventing and protecting brain damage from ischemia/reperfusion injury. In our previous
studies, we found that plant-produced asialo-rhuEPO (asialo-rhuEPOP) is non-erythropoietic and
displays excellent neuroprotective effects in a young mouse model of middle cerebral artery
occlusion (MCAO) I/R injury. Our previous studies have set the stage for the current proposed
research activities. In this SC1 renewal application, we propose to extend asialo-rhuEPOP-mediated
neuroprotection studies to aged mice, evaluate long-term neurological outcomes in both young and
aged mice, and further understand its neuroprotective mechanisms.