Metal homeostasis in the central nervous system (CNS) is a crucial component of healthy brain function, because metals serve as enzymatic cofactors and are key components of intra- and inter-neuronal signaling. Metal dysregulation wreaks havoc on neural networks via induction and proliferation of pathological pathways that cause oxidative stress, synaptic impairment, and ultimately, cognitive deficits. Thus, exploration of metal biology in relation to neurodegenerative pathology is essential in pursuing novel therapies for Alzheimer's Disease and other neurodegenerative disorders. This review covers mechanisms of action of aluminum, iron, copper, and zinc ions with respect to the progressive, toxic accumulation of extracellular β-amyloid plaques and intracellular hyperphosphorylated neurofibrillary tau tangles that characterizes Alzheimer's Disease, with the goal of evaluating the therapeutic potential of metal ion interference in neurodegenerative disease prevention and treatment. As neuroscientific interest in the role of metals in neurodegeneration escalates-in large part due to emerging evidence substantiating the interplay between metal imbalances and neuropathology-it becomes clear that the use of metal chelating agents may be a viable method for ameliorating Alzheimer's Disease pathology, as its etiology remains obscure. We conclude that, although metal therapies can potentially deter neurodegenerative processes, the most promising treatments will remain elusive until further understanding of neurodegenerative etiology is achieved. New research directions may best be guided by animal models of neurodegeneration, which reveal specific insights into biological mechanisms underlying dementia.

中文翻译：

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金属在阿尔茨海默病中的作用。

中枢神经系统 (CNS) 中的金属稳态是健康大脑功能的关键组成部分，因为金属充当酶促辅助因子并且是神经元内和神经元间信号传导的关键组成部分。金属失调通过诱导和增殖导致氧化应激、突触障碍并最终导致认知缺陷的病理途径对神经网络造成严重破坏。因此，探索与神经退行性疾病相关的金属生物学对于寻求阿尔茨海默病和其他神经退行性疾病的新疗法至关重要。这篇综述涵盖了铝、铁、铜和锌离子在细胞外 β-淀粉样蛋白斑块和细胞内过度磷酸化的神经原纤维 tau 缠结（阿尔茨海默氏症的特征）进行性、毒性积累方面的作用机制。s 疾病，目的是评估金属离子干扰在神经退行性疾病预防和治疗中的治疗潜力。随着神经科学对金属在神经退行性变中作用的兴趣不断升级——很大程度上是由于新出现的证据证实了金属失衡和神经病理学之间的相互作用——很明显，使用金属螯合剂可能是改善阿尔茨海默病病理学的一种可行方法，因为其病因仍然不明。我们得出的结论是，尽管金属疗法可以潜在地阻止神经退行性过程，但在进一步了解神经退行性病因之前，最有希望的治疗方法仍然难以捉摸。新的研究方向可能最好以神经退行性动物模型为指导，