Brain iron is a crucial participant and regulator of normal physiological activity. However, excess iron is involved in the formation of free radicals, and has been associated with oxidative damage to neuronal and other brain cells. Abnormally high brain iron levels have been observed in various neurodegenerative diseases, including neurodegeneration with brain iron accumulation, Alzheimer's disease, Parkinson's disease and Huntington's disease. However, the key question of why iron levels increase in the relevant regions of the brain remains to be answered. A full understanding of the homeostatic mechanisms involved in brain iron transport and metabolism is therefore critical not only for elucidating the pathophysiological mechanisms responsible for excess iron accumulation in the brain but also for developing pharmacological interventions to disrupt the chain of pathological events occurring in these neurodegenerative diseases. Numerous studies have been conducted, but to date no effort to synthesize these studies and ideas into a systematic and coherent summary has been made, especially concerning iron transport across the luminal (apical) membrane of the capillary endothelium and the membranes of different brain cell types. Herein, we review key findings on brain iron transport, highlighting the mechanisms involved in iron transport across the luminal (apical) as well as the abluminal (basal) membrane of the blood–brain barrier, the blood–cerebrospinal fluid barrier, and iron uptake and release in neurons, oligodendrocytes, astrocytes and microglia within the brain. We offer suggestions for addressing the many important gaps in our understanding of this important topic, and provide new insights into the potential causes of abnormally increased iron levels in regions of the brain in neurodegenerative disorders.

中文翻译：

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脑铁转运

脑铁是正常生理活动的重要参与者和调节剂。然而，过量的铁参与自由基的形成，并与神经元和其他脑细胞的氧化损伤有关。在各种神经退行性疾病中观察到异常高的脑铁水平，包括脑铁积累的神经变性、阿尔茨海默病、帕金森病和亨廷顿病。然而，为什么大脑相关区域的铁水平会增加的关键问题仍有待回答。因此，全面了解参与脑铁转运和代谢的稳态机制不仅对于阐明导致大脑中过量铁积累的病理生理机制至关重要，而且对于开发药物干预措施以破坏发生在这些神经退行性疾病中的病理事件链也至关重要. 已经进行了大量研究，但迄今为止还没有努力将这些研究和想法综合成系统和连贯的总结，特别是关于铁跨毛细血管内皮的腔（顶端）膜和不同脑细胞类型的膜的转运. 在此，我们回顾了有关脑铁转运的主要发现，强调了铁在血脑屏障、血脑脊液屏障的管腔（顶端）和腔外（基底）膜之间转运的机制，以及铁在神经元、少突胶质细胞、星形胶质细胞和小胶质细胞中的摄取和释放大脑。我们提供建议以解决我们对这一重要主题的理解中的许多重要差距，并提供有关神经退行性疾病大脑区域铁水平异常升高的潜在原因的新见解。