Hernández Carolina Castillo, Burgos Carlos Felipe, Gajardo Angela Hidalgo, Silva-Grecchi Tiare, Gavilan Javiera, Toledo Jorge Roberto, Fuentealba Jorge
Laboratory of Screening of Neuroactive Compounds, Department of Physiology, School of Biological Sciences, University of Concepción, Concepción, Chile.
Laboratory of Biotechnology and Biopharmaceutical, Department of Pathophysiology, School of Biological Sciences, University of Concepción, Concepción, Chile.
Neural Regen Res. 2017 Sep;12(9):1381-1389. doi: 10.4103/1673-5374.215240.
Erythropoietin (Epo) is a fundamental hormone in the regulation of hematopoiesis, and other secondary roles mediated by the binding of the hormone to its specific receptor (EpoR), which leads to an activation of key signaling pathways that induce an increase in cell differentiation, apoptosis control and neuroprotection. It has been suggested that their function depends on final conformation of glycosylations, related with affinity to the receptor and its half-life. The presence of EpoR has been reported in different tissues including central nervous system, where it has been demonstrated to exert a neuroprotective function against oxidative stress conditions, such as ischemic injury and neurodegenerative diseases. There is also evidence of an increase in EpoR expression in brain cell lysates of Alzheimer's patients with respect to healthy patients. These results are related with extensive experimental data of neuroprotection obtained from cell lines, primary cell cultures and hippocampal slices. Additionally, this data is correlated with experiments (water maze test) in mouse models of Alzheimer's disease where Epo treatment improved cognitive function. These studies support the idea that receptor activation induces a neuroprotective effect in neurodegenerative disorders including dementias, and especially Alzheimer's disease. Taken together, available evidence suggests that Epo appears to be a central element for EpoR activation and neuroprotective properties in the central nervous system. In this review, we will describe the mechanisms associated with neuroprotection and its relation with the activation of EpoR in order with identify new targets to develop pharmacological strategies.
促红细胞生成素（Epo）是调节造血作用的一种重要激素，它还通过与特异性受体（EpoR）结合发挥其他次要作用，这会导致关键信号通路的激活，进而促使细胞分化增加、控制细胞凋亡并实现神经保护。有人提出，其功能取决于糖基化的最终构象，这与受体亲和力及其半衰期相关。据报道，EpoR存在于包括中枢神经系统在内的不同组织中，在中枢神经系统中已证实它能对氧化应激状况（如缺血性损伤和神经退行性疾病）发挥神经保护作用。还有证据表明，与健康患者相比，阿尔茨海默病患者脑细胞裂解物中的EpoR表达增加。这些结果与从细胞系、原代细胞培养物和海马切片获得的大量神经保护实验数据相关。此外，这些数据与阿尔茨海默病小鼠模型中的实验（水迷宫试验）相关，在该实验中Epo治疗改善了认知功能。这些研究支持了这样一种观点，即受体激活在包括痴呆症尤其是阿尔茨海默病在内的神经退行性疾病中诱导产生神经保护作用。综上所述，现有证据表明，Epo似乎是中枢神经系统中EpoR激活和神经保护特性的核心要素。在本综述中，我们将描述与神经保护相关的机制及其与EpoR激活的关系，以便确定开发药理学策略的新靶点。
