Existing therapies for Parkinson’s disease (PD) are only symptomatic. As erythropoietin (EPO) is emerging for its benefits in neurodegenerative diseases, here, we test the protective effect driven by EPO in in vitro (SH-SY5Y cells challenged by MPP⁺) and in vivo (C57BL/6J mice administered with MPTP) PD models. EPO restores cell viability in both protective and restorative layouts, enhancing the dopaminergic recovery. Specifically, EPO rescues the PD-induced damage to mitochondria, as shown by transmission electron microscopy, Mitotracker assay and PINK1 expression. Moreover, EPO promotes a rescue of mitochondrial respiration while markedly enhancing the glycolytic rate, as shown by the augmented extracellular acidification rate, contributing to elevated ATP levels in MPP⁺-challenged cells. In PD mice, EPO intrastriatal infusion markedly improves the outcome of behavioral tests. This is associated with the rescue of dopaminergic markers and decreased neuroinflammation. This study demonstrates cellular and functional recovery following EPO treatment, likely mediated by the 37 Kda isoform of the EPO-receptor. We report for the first time, that EPO-neuroprotection is exerted through restoring ATP levels by accelerating the glycolytic rate. In conclusion, the redox imbalance and neuroinflammation associated with PD may be successfully treated by EPO.

中文翻译：

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线粒体代谢作为促红细胞生成素在帕金森氏病中神经保护作用的靶点

帕金森氏病（PD）的现有疗法只是对症治疗。由于促红细胞生成素（EPO）因其在神经退行性疾病中的益处而不断涌现，因此，在这里，我们测试了EPO在体外（对MPP ⁺攻击的SH-SY5Y细胞）和体内（对MP57给药的C57BL / 6J小鼠）PD的保护作用楷模。EPO可在保护性和修复性布局中恢复细胞活力，从而增强多巴胺能恢复。具体来说，EPO可以挽救PD诱导的线粒体损伤，如透射电镜，Mitotracker分析和PINK1表达所示。此外，EPO促进了线粒体呼吸的挽救，同时显着提高了糖酵解速率，如增加的细胞外酸化速率所表明的那样，有助于提高MPP ^+中的ATP水平挑战的细胞。在PD小鼠中，EPO纹状体内输注可显着改善行为测试的结果。这与多巴胺能标志物的抢救和减少神经炎症有关。这项研究表明EPO治疗后细胞和功能的恢复，可能是由EPO受体的37 Kda亚型介导的。我们首次报道，EPO神经保护作用是通过加速糖酵解速率来恢复ATP水平而发挥的。总之，EPO可以成功治疗与PD相关的氧化还原失衡和神经炎症。