![]() ![]() ![]() After intranasal administration, the molecule reaches the brain rapidly and does not stimulate erythropoiesis after acute treatments. Neuro-EPO is rapidly degraded in the liver and must be preferentially applied by intranasal route (García-Rodriguez and Sosa-Teste, 2009). It is characterized by its low sialic acid content and consequently Neuro-EPO is devoid of erythropoietic activity, while it exhibits high neuroprotective properties (Rodríguez-Cruz et al., 2010). Neuro-EPO is a recombinant human glycoprotein produced in Chinese hamster ovary cells supplied by the Center of Molecular Immunology (CIM, Havana, Cuba). In this sense, it is important to develop non-erythropoietic variant of EPO, ideally with minor chemical modifications, and Neuro-EPO appears as a promising derivative that meets these requirements. ![]() Moreover, given the pleiotropic actions of EPO in the mammalian brain, any dysbalance due to alterations in either its synthesis or its regulation could in turn produce a progressive damage in the brain region involved, leading with time to different clinical manifestations (Broxmeyer, 2013). To address this issue, an approach may be the use of non-hematopoietic EPO derivatives that retain neuroprotective activity against neuronal injury (Leist et al., 2004) but appear devoid of erythropoietic activity. The use of rh-EPO in the treatment of neurological diseases requires higher doses and prolonged application, in a way that likely produces an increase of hematocrit and blood viscosity, finally leading to serious cardiovascular events such as infarct or stroke. This was partly due to the erythropoietic effect of EPO, with a high percentage of patients showing edema and cerebral hemorrhage (Ehrenreich et al., 2009). After some encouraging initial results in clinical trials to human patients with ischemic stroke, a German multicenter EPO trial fails to detect beneficial effects. The fact that EPO was widely used in clinical practice makes rh-EPO a highly attractive candidate drug for neuroprotection/neurodegeneration. In addition, many studies have shown that EPO also possesses various other non-hematopoietic biological functions, such as neuroprotection, neurogenesis and angiogenesis. In the last 30 years, recombinant human EPO (rh-EPO) and its analogues have improved the quality of life of more than a million patients with anemia associated with chronic renal failure. The overall composition of mature EPO is ~60% protein and 40% carbohydrate, containing four glycosylated chains including three N-linked and one O-linked acidic oligosaccharide side chains that are important for the biological activity of EPO. EPO is a single polypeptide chain of 165 amino acids with a molecular mass of 30 kDa, depending on the carbohydrate content. Excitotoxicity is defined as cell death due to excessive stimulation of neurons by excitatory amino acids neurotransmitters, particularly glutamate.ĮPO is a glycoprotein cytokine, initially known for its essential role in the regulation of erythropoiesis. Although each of these different neuropathologies has a different etiology, they all share excitotoxicity as one of the main mechanisms that leads to neuronal cell loss (Dong et al., 2009). Since then, neuroprotective effects of EPO in preclinical studies have been widely reported for a variety of neurodegenerative diseases, including stroke, Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. In clinical use and neuroscience research, a solution for an effective diagnosis is in progress, but a prophylactic treatment to counteract this long-lasting plague for humanity is still unidentified.Īt the end of the 20 th century, it is known that brain cells de novo synthesize erythropoietin (EPO) and that the cytokine has neuroprotective effects against brain damage caused by permanent focal ischemia in mice (Morishita et al., 1997). Currently, neurodegenerative diseases are currently the leading cause of death and disability worldwide. The average life expectancy currently estimated for men is ~69 years, with strong differences among countries. Our common home, planet Earth, is inhabited by more than 7 billion human beings. ![]()
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