Mechanisms of divalent metal toxicity in affective disorders.
Mechanisms of divalent metal toxicity in affective disorders.
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DOI：
10.1016/j.tox.2015.11.001
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发表时间：
2016-01-02
期刊：
影响因子：
4.5
通讯作者：
Kim J
中科院分区：
文献类型：
--
作者：
Menon AV;Chang J;Kim J
金属对于大脑的正常发育是必需的，并且在许多神经生物学功能中发挥重要作用。二价金属转运体1（DMT1）是一种主要的金属转运体，参与铁和锰等几种必需金属的吸收和代谢。然而，非必需的二价金属也通过这种转运体运输。因此，DMT1表达的改变会改变有毒金属的吸收以及金属诱导的毒性。越来越多的证据表明，大脑中金属储存的增加与金属催化氧化还原反应的能力所介导的氧化应激升高有关，从而导致神经行为功能异常和神经退行性疾病的进展。金属过载也与情绪行为受损有关，尽管其潜在机制尚未完全了解，相关信息有限。目前的综述重点关注与DMT1转运的金属代谢失衡相关的精神功能障碍。关于金属过载对行为的毒性作用及其潜在毒性机制的研究可以为治疗金属相关的情感障碍提供几个新的治疗靶点。
Metals are required for proper brain development and play an important role in a number of neurobiological functions. The Divalent Metal Transporter 1 (DMT1) is a major metal transporter involved in the absorption and metabolism of several essential metals like iron and manganese. However, non-essential divalent metals are also transported through this transporter. Therefore, altered expression of DMT1 can modify the absorption of toxic metals and metal-induced toxicity. An accumulating body of evidence has suggested that increased metal stores in the brain are associated with elevated oxidative stress mediated by the ability of metals to catalyze redox reactions, resulting in abnormal neurobehavioral function and the progression of neurodegenerative diseases. Metal overload has also been implicated in impaired emotional behavior, although the underlying mechanisms are not well understood with limited information. The current review focuses on psychiatric dysfunction associated with imbalanced metabolism of metals that are transported by DMT1. The investigations with respect to the toxic effects of metal overload on behavior and their underlying mechanisms of toxicity could provide several new therapeutic targets to treat metal-associated affective disorders.