Erythropoietin increases neuronal NDPKA expression, and NDPKA up-regulation as well as exogenous application protects cortical neurons from in vitro ischemia-related insults.

Using proteomics, we identified nucleoside diphosphate kinase A also known as NME/NM23 nucleoside diphosphate kinase 1: NME1) to be up-regulated in primary cortical neuronal cultures by erythropoietin (EPO) preconditioning. To investigate a neuroprotective role of in neurons, we used a construct to knock-down and an adenoviral vector to overexpress the protein in cortical neuronal cultures prior to exposure to three ischemia-related injury models; excitotoxicity (L-glutamic acid), oxidative stress (hydrogen peroxide), and in vitro ischemia (oxygen-glucose deprivation). NDduanyu1529 down-regulation had no effect on neuronal viability following injury. By contrast, NDduanyu1529 up-regulation increased neuronal survival in all three-injury models. Similarly, treatment with NDduanyu1529 recombinant protein increased neuronal survival, but only against in vitro ischemia and excitotoxicity. These findings indicate that the NDduanyu1529 protein may confer a neuroprotective advantage following injury. Furthermore, as exogenous NDduanyu1529 protein was neuroprotective, it suggests that a cell surface receptor may be activated by NDduanyu1529 leading to a protective cell-signaling response. Taken together both intracellular and extracellular neuroprotective actions suggest that the protein is a legitimate therapeutic target for the design of drugs to limit neuronal death following stroke and other forms of brain injury.

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