Erythropoietin (EPO) is a 30-kDa molecular weight glycoprotein of 165 amino acids, coded by the EPO gene, located on Chromosome 7 (Law et al., 1986). EPO presents one small O-linked glycan and three tetra-antennary N-linked polysaccharide units, fundamental for its secretion, molecular stability, and binding to its receptor, erythropoietin receptor (EPOR; Tsuda et al., 1988). EPO is a type I cytokine essential for erythroid development and maturation (Brines and Cerami, 2005). Its expression is canonically induced by both hypoxia-inducible factor-1 (HIF-1) and HIF-2 (Keswani et al., 2011; Maiese et al., 2012), transduction factors sensitive to hypoxia and anemia. EPO expression is thus activated during the hematopoiesis process, where it coordinates the hormonal modulation on the hematopoietic system (Jelkmann, 2001). EPO’s main site of production changes throughout human life. During fetal development, blood cells are produced in the liver, and EPO is produced locally in this organ. After birth, the major EPO’s production site becomes the kidney peritubular cells (Jelkmann, 2001). Secondary EPO production sites have been described, and EPO’s expression in organs other than the kidney accounts for about 15% to 20% of the total production throughout the organism (Ponce et al., 2013). Although the kidney peritubular interstitial cells remain the main site of EPO production and secretion, a more pleiotropic role for EPO has been demonstrated in studies showing its expression in the endothelium and in the central nervous system (CNS; Anagnostou et al., 1990; Digicaylioglu et al., 1995; Marti et al., 1996). Within the CNS, EPO’s production and secretion has been demonstrated in the hippocampus, cortex, and midbrain. Furthermore, in the development of the brain and vascular system, EPO has been demonstrated to have a relevant function in promoting and stimulating neurogenesis (Shingo et al., 2001; Lombardero et al., 2011). Moreover, EPO limits cell injury and blocks the production of reactive oxygen species (ROS; Dang et al., 2010). Its neuroprotective effect and its role in counteracting oxidative stress indicate a potential beneficial effect for the molecule in the treatment of neurodegenerative diseases. EPO is currently the most sold biopharmaceutical product worldwide according to the Food and Drug Administration, and in particular, recombinant human EPO (rhEPO) is indicated in the treatment of anemic patients and diseases associated with low concentrations of EPO in plasma (European Medicines Agency; U.S. Food and Drug Administration; Ng et al., 2003). Remarkably, these patients show significant cognitive improvements, leading to the conjecture that EPO could be used for the treatment of neurodegenerative diseases (Sargin et al., 2011).

中文翻译：

---

促红细胞生成素作为一种神经保护分子：在神经退行性疾病中治疗潜力的概述。

促红细胞生成素（EPO）是位于染色体7上的30 kDa分子量的165个氨基酸的糖蛋白，由EPO基因编码（Law等，1986）。EPO提供一个小的O-连接的聚糖和三个四触角的N-连接的多糖单元，这是其分泌，分子稳定性以及与其受体促红细胞生成素受体结合的基础（EPOR； Tsuda等，1988）。EPO是红细胞发育和成熟必不可少的I型细胞因子（Brines和Cerami，2005）。缺氧诱导因子-1（HIF-1）和HIF-2（Keswani等，2011； Maiese等，2012）是对缺氧和贫血敏感的转导因子，可正常诱导其表达。因此，EPO表达在造血过程中被激活，其在造血系统上协调激素调节（Jelkmann，2001）。EPO的主要生产地点在整个人类生活中都会发生变化。在胎儿发育过程中，肝脏会产生血细胞，而EPO则在该器官中局部产生。出生后，EPO的主要生产部位变成了肾小管周围细胞（Jelkmann，2001）。已经描述了次要的EPO生产位点，并且在整个肾脏中，EPO在肾脏以外的器官中的表达约占总产量的15％至20％（Ponce等人，2013）。尽管肾小管间质细胞仍然是EPO产生和分泌的主要部位，但在研究表明EPO在内皮和中枢神经系统中表达的研究中已证明EPO具有更强的作用（CNS; Anagnostou等，1990; Digicaylioglu等人，1995； Marti等，1996）。在CNS中，EPO的产生和分泌已在海马，皮层和中脑得到证实。此外，在脑和血管系统的发育中，EPO已被证明具有促进和刺激神经发生的相关功能（Shingo等，2001； Lombardero等，2011）。此外，EPO限制了细胞损伤并阻止了活性氧的产生（ROS； Dang等，2010）。它的神经保护作用及其在抵抗氧化应激中的作用表明该分子在治疗神经退行性疾病中具有潜在的有益作用。根据美国食品药品监督管理局（FDA），EPO目前是全球销量最高的生物制药产品，尤其是 重组人EPO（rhEPO）用于贫血患者和与血浆中EPO浓度低相关的疾病（欧洲药品管理局；美国食品药品监督管理局； Ng等，2003）。值得注意的是，这些患者表现出明显的认知改善，从而推测EPO可用于治疗神经退行性疾病（Sargin等，2011）。