Targeting erythropoietin for chronic neurodegenerative diseases

Introduction: Since erythropoietin (EPO) and EPO receptor (EPOR) are expressed in the central nervous system (CNS) beyond hematopoietic system, EPO illustrates a robust biological function in maintaining neuronal survival and regulating neurogenesis and may play a crucial role in neurodegenerative diseases. Areas covered: EPO is capable of modulating multiple cellular signal transduction pathways to promote neuronal survival and enhance the proliferation and differentiation of neuronal progenitor cells. Initially, EPO binds to EPOR to activate the Janus-tyrosine kinase 2 (Jak2) protein followed by modulation of protein kinase B (Akt), mammalian target of rapamycin, signal transducer and activators of transcription 5, mitogen-activated protein kinases, protein tyrosine phosphatases, Wnt1 and nuclear factor-kappa B. As a result, EPO may actively prevent the progression of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis and motor neuron diseases. Expert opinion: Novel knowledge of the cell signaling pathways regulated by EPO in the CNS will allow us to establish the foundation for the development of therapeutic strategies against neurodegenerative diseases. Further investigation of the role of EPO in neurodegenerative diseases can not only formulate EPO as a therapeutic candidate, but also further identify novel therapeutic targets for these disorders.