Copper (Cu) and iron (Fe) are redox active metals essential for the regulation of cellular pathways that are fundamental for brain function, including neurotransmitter synthesis and release, neurotransmission, and protein turnover. Cu and Fe are tightly regulated by sophisticated homeostatic systems that tune the levels and localization of these redox active metals. The regulation of Cu and Fe necessitates their coordination to small organic molecules and metal chaperone proteins that restrict their reactions to specific protein centres, where Cu and Fe cycle between reduced (Fe²⁺, Cu⁺) and oxidised states (Fe³⁺, Cu²⁺). Perturbation of this regulation is evident in the brain affected by neurodegeneration. Here we review the evidence that links Cu and Fe dyshomeostasis to neurodegeneration as well as the promising preclinical and clinical studies reporting pharmacological intervention to remedy Cu and Fe abnormalities in the treatment of Alzheimer’s disease (AD), Parkinson’s disease (PD) and Amyotrophic lateral sclerosis (ALS).

中文翻译：

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神经退行性疾病中的氧化还原活性金属。

铜（Cu）和铁（Fe）是氧化还原活性金属，对于调节对大脑功能至关重要的细胞途径（包括神经递质的合成和释放，神经传递和蛋白质更新）至关重要。铜和铁受到精密的稳态系统的严格调节，该系统可调节这些氧化还原活性金属的含量和位置。铜和铁的调节要求它们与有机小分子和金属伴侣蛋白协调，从而将它们的反应限制在特定的蛋白质中心，其中铜和铁在还原态（Fe 2 ⁺，Cu ⁺）和氧化态（Fe ³⁺，Cu ²⁺）。这种调节的微扰在受神经变性影响的大脑中很明显。在这里，我们回顾了将铜和铁异常动态与神经变性联系起来的证据，以及有前途的临床前和临床研究，报告了药理学干预以补救铜和铁异常，以治疗阿尔茨海默氏病（AD），帕金森氏病（PD）和肌萎缩性侧索硬化（ALS）。