Elevated iron and decreased copper levels are cardinal features of the degenerating substantia nigra pars compacta in the Parkinson’s disease brain. Both of these redox-active metals, and fellow transition metals manganese and zinc, are found at high concentrations within the midbrain and participate in a range of unique biological reactions. We examined the total metal content and cellular compartmentalisation of manganese, iron, copper and zinc in the degenerating substantia nigra, disease-affected but non-degenerating fusiform gyrus, and unaffected occipital cortex in the post mortem Parkinson’s disease brain compared with age-matched controls. An expected increase in iron and a decrease in copper concentration was isolated to the soluble cellular fraction, encompassing both interstitial and cytosolic metals and metal-binding proteins, rather than the membrane-associated or insoluble fractions. Manganese and zinc levels did not differ between experimental groups. Altered Fe and Cu levels were unrelated to Braak pathological staging in our cases of late-stage (Braak stage V and VI) disease. The data supports our hypothesis that regional alterations in Fe and Cu, and in proteins that utilise these metals, contribute to the regional selectively of neuronal vulnerability in this disorder.

中文翻译：

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帕金森病大脑中铜、铁、锰和锌的亚细胞区室化


铁含量升高和铜含量降低是帕金森病患者大脑中黑质致密部退化的主要特征。这两种氧化还原活性金属以及其他过渡金属锰和锌在中脑内浓度很高，并参与一系列独特的生物反应。我们检查了帕金森病死后大脑中退化黑质、受疾病影响但未退化的梭状回和未受影响的枕叶皮层中锰、铁、铜和锌的总金属含量和细胞区划，与年龄匹配的对照进行比较。预期的铁浓度增加和铜浓度降低被分离到可溶性细胞部分，包括间质和胞质金属以及金属结合蛋白，而不是膜相关或不溶性部分。实验组之间的锰和锌水平没有差异。在我们的晚期（布拉克第五期和第六期）疾病病例中，铁和铜水平的改变与布拉克病理分期无关。这些数据支持了我们的假设，即铁和铜以及利用这些金属的蛋白质的区域变化导致了这种疾病中神经元脆弱性的区域选择性。