Carbamoylated erythropoietin induces a neurotrophic gene profile in neuronal cells

Progress in Neuro-psychopharmacology & Biological Psychiatry
Neeraj K TiwariSamuel S Newton

Abstract

Erythropoietin (EPO), a cytokine molecule, is best-known for its role in erythropoiesis. Preclinical studies have demonstrated that EPO has robust neuroprotective effects that appear to be independent of erythropoiesis. It is also being clinically tested for the treatment of neuropsychiatric illnesses due to its behavioral actions. A major limitation of EPO is that long-term administration results in excessive red blood cell production and increased blood viscosity. A chemical modification of EPO, carbamoylated erythropoietin (CEPO), reproduces the behavioral response of EPO in animal models but does not stimulate erythropoiesis. The molecular mechanisms involved in the behavioral effects of CEPO are not known. To obtain molecular insight we examined CEPO induced gene expression in neuronal cells. PC-12 cells were treated with CEPO followed by genome-wide microarray analysis. We investigated the functional significance of the gene profile by unbiased bioinformatics analysis. The Ingenuity pathway analysis (IPA) software was employed. The results revealed activation of functions such as neuronal number and long-term potentiation. Regulated signaling cascades included categories such as neurotrophin, CREB, NGF and synaptic long-t...Continue Reading

Associated Datasets

Citations

Jan 5, 2021·Frontiers in Neuroscience·Hui WangAi-Min Wu
Dec 12, 2020·Drug Design, Development and Therapy·Nicholas J PekasSamuel S Newton
Apr 25, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Inês SilvaVanessa Mateus
Jul 20, 2021·Journal of Neurochemistry·Daniela C VittoriAlcira B Nesse

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