铁调素和铁相关神经退行性疾病

Hepcidin and Iron-associated Neurodegenerative Disorders

脑铁异常增高至少是部分神经退行性疾病如阿尔茨海默氏病和帕金森病等发生的一个起因。铁调素通过与膜铁转运蛋白1(ferroportin 1,Fpn1)结合,导致其内吞和降解,抑制十二指肠铁吸收和巨噬细胞铁的释放,调节机体铁稳态。因此,铁调素(hepcidin)是这些疾病药物干预的一个新靶点。在所有与铁相关的神经退行性疾病中,将铁恢复至正常水平或阻止脑铁增加是一种潜在的治疗策略。最近研究表明,脑中铁调素水平升高可抑制血脑屏障、神经元和星形胶质细胞中铁转运蛋白的表达,进而显著降低脑铁含量。该综述主要讨论铁调素在脑中的表达调控作用及其在疾病中潜在的治疗作用,为疾病的预防和治疗提供新的策略。

The abnormally increased iron in the brain is an initial cause of neuronal death at least in some neurodegenerative. By binding to a unique cellular iron exporter,ferroportin 1 result in its endocytosis and degradation,and inhibit the release of duodenal iron to plasma and inhibit the release of iron from macrophage,then regulat the iron homeostasis of the body. Therefore,hepcidin is a new target for pharmacological intervention in these diseases. Reducing iron to normal level or hampering iron to increase with age in the brain is a promising therapeutic strategy for all iron-associated neurodegenerative disorders. Recent studies demonstrated that increasing hepcidin level in the brain could significantly reduce brain iron contents by regulating the expression of iron transport proteins located in the brain-blood barrier（BBB）,neurons and astrocytes. This review mainly discusses the role of hepcidin in the brain and its potential therapeutic role in the disease,providing a new strategy for the prevention and treatment of those diseases.