Department of Biopharmaceutical Sciences, School of Pharmacy and Health Sciences, Keck Graduate Institute, 535 Watson Dr, Claremont, CA, 91711, USA.
College of Medicine, California Northstate University, Elk Grove, CA, 95757, USA.
Neuromolecular Med. 2019 Mar;21(1):12-24. doi: 10.1007/s12017-019-08524-y. Epub 2019 Jan 17.
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder in the world, and intracellular neurofibrillary tangles and extracellular amyloid-beta protein deposits represent the major pathological hallmarks of the disease. Currently available treatments provide some symptomatic relief but fail to modify primary pathological processes that underlie the disease. Erythropoietin (EPO), a hematopoietic growth factor, acts primarily to stimulate erythroid cell production, and is clinically used to treat anemia. EPO has evolved as a therapeutic agent for neurodegeneration and has improved neurological outcomes and AD pathology in rodents. However, penetration of the blood-brain barrier (BBB) and negative hematopoietic effects are the two major challenges for the therapeutic development of EPO for chronic neurodegenerative diseases like AD. The transferrin receptors at the BBB, which are responsible for transporting transferrin-bound iron from the blood into the brain parenchyma, can be used to shuttle therapeutic molecules across the BBB. In this review, we discuss the role of EPO as a potential neurotherapeutic for AD, challenges associated with EPO development for AD, and targeting the BBB transferrin receptor for EPO brain delivery.
阿尔茨海默病（AD）是世界上最常见的神经退行性疾病，细胞内神经原纤维缠结和细胞外β淀粉样蛋白沉积是该疾病的主要病理特征。目前可用的治疗方法提供了一些症状缓解，但未能改变疾病的主要病理过程。促红细胞生成素（EPO）是一种造血生长因子，主要作用是刺激红细胞生成，临床上用于治疗贫血。EPO 已发展成为神经退行性疾病的治疗药物，并在啮齿动物中改善了神经学结局和 AD 病理学。然而，血脑屏障（BBB）的穿透性和负性造血作用是 EPO 治疗 AD 等慢性神经退行性疾病的两个主要挑战。BBB 上的转铁蛋白受体负责将结合转铁蛋白的铁从血液转运到脑实质，可以用来将治疗分子穿梭过 BBB。在这篇综述中，我们讨论了 EPO 作为 AD 潜在神经治疗药物的作用、EPO 开发用于 AD 面临的挑战，以及针对 EPO 脑内传递的 BBB 转铁蛋白受体。
