title: Targeting erythropoietin for chronic neurodegenerative diseases.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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 κB. 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Medicine and Dentistry of New Jersey, Cancer Center, New Jersey NJ 07103, USA. zzchong@yahoo.com
authors.forename: Zhao Zhong
authors.initials: ZZ
authors.lastname: Chong
authors.forename: Yan Chen
authors.initials: YC
authors.lastname: Shang
authors.forename: Yanling
authors.initials: Y
authors.lastname: Mu
authors.forename: Shuxiang
authors.initials: S
authors.lastname: Cui
authors.forename: Qingqiang
authors.initials: Q
authors.lastname: Yao
authors.forename: Kenneth
authors.initials: K
authors.lastname: Maiese
mesh_terms: D000818:Animals; D002908:Chronic Disease; D015195:Drug Design; D004921:Erythropoietin / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000503:physiopathology; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D017467:Receptors, Erythropoietin; D004921:Erythropoietin