Maiese Kenneth
Cellular and Molecular Signaling, Newark, New Jersey 07101.
Front Biosci (Landmark Ed). 2016 Jan;21(3):561-596. doi: 10.2741/4408.
Globally, greater than 30 million individuals are afflicted with disorders of the nervous system accompanied by tens of thousands of new cases annually with limited, if any, treatment options. Erythropoietin (EPO) offers an exciting and novel therapeutic strategy to address both acute and chronic neurodegenerative disorders. EPO governs a number of critical protective and regenerative mechanisms that can impact apoptotic and autophagic programmed cell death pathways through protein kinase B (Akt), sirtuins, mammalian forkhead transcription factors, and wingless signaling. Translation of the cytoprotective pathways of EPO into clinically effective treatments for some neurodegenerative disorders has been promising, but additional work is necessary. In particular, development of new treatments with erythropoiesis-stimulating agents such as EPO brings several important challenges that involve detrimental vascular outcomes and tumorigenesis. Future work that can effectively and safely harness the complexity of the signaling pathways of EPO will be vital for the fruitful treatment of disorders of the nervous system.
在全球范围内,超过3000万人患有神经系统疾病,每年还有数以万计的新病例,而治疗选择(即便有)也非常有限。促红细胞生成素(EPO)为治疗急性和慢性神经退行性疾病提供了一种令人兴奋的新型治疗策略。EPO调控着许多关键的保护和再生机制,这些机制可通过蛋白激酶B(Akt)、沉默调节蛋白、哺乳动物叉头转录因子和无翅信号通路影响凋亡和自噬程序性细胞死亡途径。将EPO的细胞保护途径转化为针对某些神经退行性疾病的临床有效治疗方法已初见成效,但仍需开展更多工作。特别是,开发如EPO这样的促红细胞生成剂的新疗法带来了几个重要挑战,包括有害的血管后果和肿瘤发生。未来能够有效且安全地利用EPO信号通路复杂性的工作,对于成功治疗神经系统疾病至关重要。