Influence of multiple metal ions on β-amyloid aggregation and dissociation on a solid surface
Influence of multiple metal ions on β-amyloid aggregation and dissociation on a solid surface
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DOI：
10.1021/bi800012e
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发表时间：
2008-05-13
期刊：
影响因子：
2.9
通讯作者：
Park, Chan Beum
中科院分区：
文献类型：
--
作者：
Ryu, Jungki;Girigoswami, Koyeli;Park, Chan Beum
最近发现的证据表明，阿尔茨海默氏病（AD）中的β-淀粉样蛋白（A β）肽的沉淀和毒性是由与新皮质金属离子，特别是Zn 2+，Cu 2+和Fe 3+的异常相互作用引起的。虽然许多研究集中在“单一”金属离子的作用及其与A β肽的相互作用，但涉及“多种”金属离子的研究几乎没有探索。在此，为了探索不同金属共沉积的性质，将两种或更多种金属离子沿着A β在通过固定A β 42寡聚体制备的固体模板上孵育。通过两种方法研究了Zn 2+、Cu 2+和Fe 3+对A β聚集的影响：共孵育和顺序加入。我们的研究结果表明，使用非原位原子力显微镜，ThT诱导荧光，和FTIR光谱表明，共孵育的Cu 2+，Zn 2+，和Fe 3+显着改变聚集体的形态。混合金属离子的浓度依赖性研究表明，在比Cu 2+低得多的浓度下需要Zn 2+来产生非纤维状无定形A β沉积物。此外，在Fe ~（3+）诱导的纤维状聚集体上依次加入Zn ~（2+）或Cu ~（2+），表明Zn ~（2+）和Cu ~（2+）可能改变Fe ~（3+）诱导的聚集体的构象。我们的研究结果阐明了多种金属离子通过与A β肽或其聚集体的相互作用而共存。
Recently discovered evidences suggest that precipitation of Alzheimer's beta-amyloid (A beta) peptide and the toxicity in Alzheimer's disease (AD) are caused by abnormal interactions with neocortical metal ions, especially Zn2+, CU2+, and Fe3+. While many studies had focused on the role of a "single" metal ion and its interaction with A beta peptides, such studies involving "multiple" metal ions have hardly been explored. Here, to explore the nature of codeposition of different metals, two or more metal ions along with A beta were incubated over a solid template prepared by immobilizing A beta 42 oligomers. The influence of Zn2+, Cu2+, and Fe3+ on A beta aggregation was investigated by two approaches: co-incubation and sequential addition. Our results using ex situ AFM, ThT-induced fluorescence, and FTIR spectroscopy indicated that the co-incubation of Cu2+, Zn2+, and Fe3+ significantly altered the morphology of aggregates. A concentration dependence study with mixed metal ions suggested that Zn2+ was required at much lower concentrations than CU2+ to yield nonfibrillar amorphous A beta deposits. In addition, sequential addition of Zn2+ or Cu2+ on fibrillar aggregates formed by Fe3+ demonstrated that Zn2+ and Cu2+ could possibly change the conformation of the aggregates induced by Fe3+. Our findings elucidate the coexistence of multiple metal ions through their interactions with A beta peptides or its aggregates.