Therapeutic potential of erythropoietin and its structural or functional variants in the nervous system.
The growth factor erythropoietin (EPO) and erythropoietin receptors (EPOR) are expressed in the nervous system. Neuronal expression of EPO and EPOR peaks during brain development and is upregulated in the adult brain after injury. Peripherally administered EPO, and at least some of its variants, cross the blood-brain barrier, stimulate neurogenesis, neuronal differentiation, and activate brain neurotrophic, anti-apoptotic, anti-oxidant and anti-inflammatory signaling. These mechanisms underlie their tissue protective effects in nervous system disorders. As the tissue protective functions of EPO can be separated from its stimulatory action on hematopoiesis, novel EPO derivatives and mimetics, such as asialo-EPO and carbamoylated EPO have been developed. While the therapeutic potential of the novel EPO derivatives continues to be characterized in preclinical studies, the experimental findings in support for the use of recombinant human (rh)EPO in human brain disease have already been translated to clinical studies in acute ischemic stroke, chronic schizophrenia, and chronic progressive multiple sclerosis. In this review article, we assess the studies on EPO and, in particular, on its structural or functional variants in experimental models of nervous system disorders, and we provide a short overview of the completed and ongoing clinical studies testing EPO as neuroprotective/neuroregenerative treatment option in neuropsychiatric disease.
Sirén
Anna-Leena
AL
Department of Neurosurgery, University of Würzburg, Würzburg, 97080 Germany.
Fasshauer
Theresa
T
Bartels
Claudia
C
Ehrenreich
Hannelore
H
D000818:Animals; D001927:Brain Diseases / Q000188:drug therapy* / Q000378:metabolism; D004921:Erythropoietin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D009420:Nervous System / Q000187:drug effects*; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010525:Peripheral Nerves / Q000187:drug effects; D017467:Receptors, Erythropoietin / Q000187:drug effects; D012164:Retinal Diseases / Q000188:drug therapy / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000378:metabolism; D020521:Stroke / Q000188:drug therapy / Q000378:metabolism
D018696:Neuroprotective Agents; D017467:Receptors, Erythropoietin; D004921:Erythropoietin