Institute of Translational & Precision Medicine, Nantong University, Nantong, Jiangsu, China.
Laboratory of Neuropharmacology, School of Pharmacy & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Med Res Rev. 2020 Mar;40(2):633-653. doi: 10.1002/med.21631. Epub 2019 Aug 30.
Abnormally high brain iron, resulting from the disrupted expression or function of proteins involved in iron metabolism in the brain, is an initial cause of neuronal death in neuroferritinopathy and aceruloplasminemia, and also plays a causative role in at least some of the other neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, and Friedreich's ataxia. As such, iron is believed to be a novel target for pharmacological intervention in these disorders. Reducing iron toward normal levels or hampering the increases in iron associated with age in the brain is a promising therapeutic strategy for all iron-related neurodegenerative disorders. Hepcidin is a crucial regulator of iron homeostasis in the brain. Recent studies have suggested that upregulating brain hepcidin levels can significantly reduce brain iron content through the regulation of iron transport protein expression in the blood-brain barrier and in neurons and astrocytes. In this review, we focus on the discussion of the therapeutic potential of hepcidin in iron-associated neurodegenerative diseases and also provide a systematic overview of recent research progress on how misregulated brain iron metabolism is involved in the development of multiple neurodegenerative disorders.
异常高的大脑铁含量是神经铁蛋白病和铜蓝蛋白血症中神经元死亡的初始原因，这是由于大脑中铁代谢相关蛋白的表达或功能失调所致，它在包括阿尔茨海默病、帕金森病、亨廷顿病和弗里德里希共济失调在内的至少一些其他神经退行性疾病中也起着致病作用。因此，铁被认为是这些疾病药物干预的一个新靶点。将铁降低到正常水平或阻止大脑中铁含量随年龄的增加，这是治疗所有与铁相关的神经退行性疾病的一种有前途的治疗策略。铁调素是大脑中铁稳态的关键调节剂。最近的研究表明，通过调节血脑屏障和神经元及星形胶质细胞中铁转运蛋白的表达，上调脑铁调素水平可以显著降低脑铁含量。在这篇综述中，我们重点讨论了铁调素在与铁相关的神经退行性疾病中的治疗潜力，并系统地概述了最近关于铁代谢失调如何参与多种神经退行性疾病发展的研究进展。
