Blood-brain barrier flux of aluminum, manganese, iron and other metals suspected to contribute to metal-induced neurodegeneration.
Blood-brain barrier flux of aluminum, manganese, iron and other metals suspected to contribute to metal-induced neurodegeneration.
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DOI：
10.3233/jad-2006-102-309
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
R. Yokel
中科院分区：
文献类型：
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作者：
R. Yokel
许多神经退行性疾病的病因仅部分归因于获得性特征，这表明环境因素也可能起作用。金属稳态失调引起或已经涉及许多神经退行性疾病。金属通量通过血脑屏障（脑金属吸收的主要途径）和脉络丛以及感觉神经金属吸收从鼻腔进行审查。血脑屏障中的转运蛋白被列出，以说明将物质移入和移出大脑的广泛可能性。有争议的作用，铝在阿尔茨海默氏病，证据表明，脑铝摄取转铁蛋白受体介导的内吞作用和柠檬酸铝的系统XC;{-}和有机阴离子转运，结果表明转运介导的铝脑外流进行了审查。锰的能力，产生帕金森样综合征，转铁蛋白和非转铁蛋白依赖的机制，其中可能包括存储操作的钙通道，并缺乏转运蛋白介导的锰脑外排的锰吸收的证据进行了讨论。转铁蛋白依赖和独立的机制，脑铁摄取的证据。本文综述了铜转运蛋白ATP 7A和ATP 7 B及其在门克斯病和威尔逊病中的作用。脑锌吸收促进L-和D-组氨酸，但转运蛋白，如果参与，尚未确定。脑铅摄取可能涉及非能量依赖性过程、钙库操纵的钙通道和/或ATP依赖性钙泵。甲基汞可与L-半胱氨酸形成类似蛋氨酸的复合物，使其能够通过L系统转运。锌转运蛋白，锌转运蛋白和Zip，在调节脑锌的假定作用进行了讨论。虽然已经确定了一些金属的脑摄取机制，但从脑中流出的金属很少受到关注，从而阻止了有助于脑金属浓度的所有过程的整合。
The etiology of many neurodegenerative diseases has been only partly attributed to acquired traits, suggesting environmental factors may also contribute. Metal dyshomeostasis causes or has been implicated in many neurodegenerative diseases. Metal flux across the blood-brain barrier (the primary route of brain metal uptake) and the choroid plexuses as well as sensory nerve metal uptake from the nasal cavity are reviewed. Transporters that have been described at the blood-brain barrier are listed to illustrate the extensive possibilities for moving substances into and out of the brain. The controversial role of aluminum in Alzheimer's disease, evidence suggesting brain aluminum uptake by transferrin-receptor mediated endocytosis and of aluminum citrate by system Xc;{-} and an organic anion transporter, and results suggesting transporter-mediated aluminum brain efflux are reviewed. The ability of manganese to produce a parkinsonism-like syndrome, evidence suggesting manganese uptake by transferrin- and non-transferrin-dependent mechanisms which may include store-operated calcium channels, and the lack of transporter-mediated manganese brain efflux, are discussed. The evidence for transferrin-dependent and independent mechanisms of brain iron uptake is presented. The copper transporters, ATP7A and ATP7B, and their roles in Menkes and Wilson's diseases, are summarized. Brain zinc uptake is facilitated by L- and D-histidine, but a transporter, if involved, has not been identified. Brain lead uptake may involve a non-energy-dependent process, store-operated calcium channels, and/or an ATP-dependent calcium pump. Methyl mercury can form a complex with L-cysteine that mimics methionine, enabling its transport by the L system. The putative roles of zinc transporters, ZnT and Zip, in regulating brain zinc are discussed. Although brain uptake mechanisms for some metals have been identified, metal efflux from the brain has received little attention, preventing integration of all processes that contribute to brain metal concentrations.