帕金森氏病脑中铜，铁，锰和锌的亚细胞区划,Metallomics

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帕金森氏病脑中铜，铁，锰和锌的亚细胞区划
Metallomics ( IF 2.9 ) Pub Date : 2017-09-13 00:00:00 , DOI: 10.1039/c7mt00244k
Sian Genoud _{1,

2,

3,

4,

5} , Blaine R. Roberts _{5,

6,

7,

8} , Adam P. Gunn _{5,

6,

7,

8} , Glenda M. Halliday _{1,

2,

3,

4,

5} , Simon J. G. Lewis _{1,

2,

3,

4,

5} , Helen J. Ball _{4,

5,

9,

10} , Dominic J. Hare _{5,

6,

7,

8,

11} , Kay L. Double _{1,

2,

3,

4,

5}

Affiliation

铁的升高和铜水平的降低是帕金森氏病大脑中退化的黑质致密性黑质的主要特征。这些氧化还原活性金属以及过渡金属锰和锌都在中脑中以高浓度被发现，并参与一系列独特的生物反应。我们在验尸中检查了退化的黑质，受疾病影响但未退化的梭状回，以及未受影响的枕叶皮层中锰，铁，铜和锌的总金属含量和细胞分隔与年龄匹配的对照组相比，帕金森氏病的大脑。分离出预期的铁含量增加和铜浓度降低的可溶性细胞组分，既包括间隙金属和胞质金属，也包括金属结合蛋白，而不是膜相关组分或不溶组分。实验组之间的锰和锌水平没有差异。在我们的晚期（Braak V和VI期）疾病病例中，Fe和Cu水平的改变与Braak病理分期无关。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性改变，选择性地促进了这种疾病中神经元易损性的区域性变化。

"点击查看英文标题和摘要"

Subcellular compartmentalisation of copper, iron, manganese, and zinc in the Parkinson's disease brain

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.

更新日期：2017-09-25

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