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・ Erythropoietic porphyria
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・ Erythropoietin
Erythropoietin in neuroprotection
・ Erythropoietin receptor
・ Erythropotamos
・ Erythropterus
・ Erythropterus amabilis
・ Erythropterus boliviensis
・ Erythropterus cuissi
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・ Erythrose
・ Erythrose 4-phosphate
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・ Erythroseris
・ Erythroseris amabilis


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Erythropoietin in neuroprotection : ウィキペディア英語版
Erythropoietin in neuroprotection
Erythropoietin in neuroprotection is the use of the glycoprotein erythropoietin (Epo) for neuroprotection. Epo controls erythropoiesis, or red blood cell production.
Erythropoietin and its receptor are both present in the central nervous system with erythropoietin alpha capable of crossing the blood brain barrier via active transport. The presence of Epo within the spinal fluid of infants and the expression of Epo-R in the spinal cord, suggesting a role by Epo within the CNS. Epo and Epo-R is expressed in the mammalian retina, and therefore Epo represents a potential therapy to protect photoreceptors damaged from hypoxic pretreatment.
Erythropoietin has been shown to protect nerve cells from hypoxia-induced glutamate toxicity.〔 Acute hypoxia inducement in the adult mouse retina stimulates expression of Epo in addition to other growth factors. Epo response is stimulated by hypoxia and is capable of protecting against apoptosis of erythroid progenitors via a mechanism that is described in the Mechanism of Action section.〔 Epo-R is present in cultured hippocampal and cerebral cortical neurons isolated from rat embryos. Epo was capable of protecting the cultured neurons from glutamate neurotoxicity after only a short exposure. It was concluded that Epo-mediated increase in intracellular calcium concentration is indicative of Epo's neuroprotective role after CNS-related hypoxia or ischemia.〔
Erythropoietin’s role in reducing immune response has been described recently by Michael Brines through his research in administering recombinant human Epo into the blood circulation, which was translocated to the cerebrospinal fluid. RhEpo administer in rats prevented apoptosis of neurons during a cerebral arterial occlusion. It also reduced infarction volume by 75% and decreased post-infarct inflammation.
Epo has also been demonstrated to enhance nerve recovery after spinal trauma. Celik and associates investigated motor neuron apoptosis in rabbits with a transient global spinal ischemia model. The functional neurological status of animals given RhEpo was better after recovery from anesthesia, and kept improving over a two-day period. The animals given saline demonstrated a poor functional neurological status and showed no significant improvements. These results showed that RhEpo has both an acute and delayed beneficial action in ischemic spinal cord injury.
== Development with mutant Epo and EpoR ==

While EpoR has been found in high levels in the embryonic brain, its role in brain development is unclear. Epo stimulates neural progenitor cells and prevents apoptosis in the embryonic brain in mice. Mice without EpoR demonstrated severe anemia, defective heart development, and eventually death around embryonic day 13.5 from apoptosis in the liver, endocardium, myocardium, and fetal brain. As early as embryonic day 10.5 the lack of EpoR can affect brain development by increasing fetal brain apoptosis and decreasing the number of neural progenitor cells. By exposing cultures of EpoR positive embryonic cortical neurons to stimulation by Epo administration, the cells decreased apoptosis, as opposed to the decrease in neuron generation in EpoR negative cells. The neuroprotective activity of Epo can be observed as early as embryonic day 10.5 in the developing brain and contributes to selective cell survival in the developing brain.
However it has been questioned whether EpoR may or may not be a determining factor for the nervous system function. The contribution of Epo and EpoR to neuroprotection and development are not as clearly understood as its role in erythropoiesis in hematopoietic tissue. In a line of mice that expressed EpoR exclusively in hematopoietic cells, the mice developed normally and were fertile, despite the lack of EpoR in nonhematopoietic tissue. Differential expression of EpoR between erythroid cells. Most notably, plasma Epo concentration is regulated by nonhematopoietic EpoR expression when the peak of plasma concentrations for induced anemia in mutant and wild-type mice. The expression of EpoR in nonhematopoietic tissue is dispensable in normal mouse development, but that the sensitivity of erythroid progenitors to Epo is regulated by the expression of EpoR.
Erythropoietin mutants R103-E and S100-E (though S100 in Epo doesn't exist) has been reportedto be non-erythropoietin but retain the neuroprotective function. Epo with R103 mutation is a potent inhibitor of wild type Epo from binding to its receptor. Though, the viral vector expressed R103-E Epo mutant was shown to be inhibitory to the progression / development of nervous tissue damage in many models, it is not shown to recover the nervous tissue post damage. Given the associated risks, it would be foolish to administer / express Mutant as a preventive measure from neuronal injury. Hence, from a medical or commercial point of view, safe and feasible neuro-protective Epo mutants are not possible.
It should also be noted that quite a bit of research emphesis is on non erythropoietic but, neuroprotective Peptides of Erythropoietin. Peptide of Epo with amino acids 92-111 is neuroprotective while its erythropoietic potency is 10 fold less than the wild type.
A short peptide sequence from the erythropoietin molecule called JM4, has been found to be non-erythropoietic yet neuroprotective and is being readied for Stage 1 and 2 clinical studies.〔http://link.springer.com/article/10.1007/s13311-015-0379-1〕〔(【引用サイトリンク】 Short Stabilized EPO-Peptide as Side-Effect-Free Therapeutic Agents for Multiple Sclerosis and Acute Brain Trauma )

抄文引用元・出典: フリー百科事典『 ウィキペディア(Wikipedia)
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