Regulation of brain iron and copper homeostasis by brain barrier systems: implication in neurodegenerative diseases.
Regulation of brain iron and copper homeostasis by brain barrier systems: implication in neurodegenerative diseases.
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DOI：
10.1016/j.pharmthera.2011.10.006
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发表时间：
2012-02
影响因子：
13.5
通讯作者：
Monnot, Andrew D.
中科院分区：
文献类型：
--
作者：
Zheng, Wei;Monnot, Andrew D.
关键词：
铁(Fe)和铜(Cu)对神经元功能是必不可少的；已知两者中任何一种的过量或缺乏都是几种常见的神经退行性疾病的病因。铁和铜在中枢环境中的这种微妙平衡是由脑屏障系统维持的，即血液和脑间质液体之间的血脑屏障(BBB)和血液和脑脊液(CSF)之间的血脑脊液屏障(BCB)。本文就脑屏障系统的结构和功能特点作一简要介绍。目前对铁和铜跨脑屏障运输的理解被彻底考察，主要集中在血脑屏障和血脑屏障是否协调铁和铜在血液和脑/脑脊液之间的流动方向。特别是，探讨了屏障中的相关金属转运体，如转铁蛋白受体(TFR)、二价金属转运体(DMT1)、铜转运体(CTR1)、ATP7A/B和铁蛋白(FPN)调节金属跨屏障运动的机制。最后，讨论了由于内源性紊乱或外源性侮辱，大脑屏障导致的金属运输功能障碍的有害后果。了解中枢神经系统中铁和铜的动态平衡调节有助于设计针对大脑屏障调节蛋白的新药，用于治疗金属缺乏或过载相关的神经系统疾病。
Iron (Fe) and copper (Cu) are essential to neuronal function; excess or deficiency of either is known to underlie the pathoetiology of several commonly known neurodegenerative disorders. This delicate balance of Fe and Cu in the central milieu is maintained by the brain barrier systems, i.e., the blood-brain barrier (BBB) between the blood and brain interstitial fluid and the blood- cerebrospinal fluid barrier (BCB) between the blood and cerebrospinal fluid (CSF). This review provides a concise description on the structural and functional characteristics of the brain barrier systems. Current understanding of Fe and Cu transport across the brain barriers is thoroughly examined, with major focuses on whether the BBB and BCB coordinate the direction of Fe and Cu fluxes between the blood and brain/CSF. In particular, the mechanism by which pertinent metal transporters in the barriers, such as the transferrin receptor (TfR), divalent metal transporter (DMT1), copper transporter (CTR1), ATP7A/B, and ferroportin (FPN), regulate metal movement across the barriers is explored. Finally, the detrimental consequences of dysfunctional metal transport by brain barriers, as a result of endogenous disorders or exogenous insults, are discussed. Understanding the regulation of Fe and Cu homeostasis in the central nervous system aids in the design of new drugs targeted on the regulatory proteins at the brain barriers for the treatment of metal’s deficiency or overload-related neurological diseases.
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