Metal ions differentially influence the aggregation and deposition of Alzheimer's β-amyloid on a solid template
Metal ions differentially influence the aggregation and deposition of Alzheimer's β-amyloid on a solid template
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DOI：
10.1021/bi7000032
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发表时间：
2007-05-22
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：
Ha, Chanki;Ryu, Jungki;Park, Chan Beum
β-淀粉样蛋白（A β）在脑组织的异常沉积和聚集被认为是阿尔茨海默病（AD）的特征性神经病理学特征之一。环境条件如金属离子、pH和细胞膜与A β沉积和斑块形成相关。根据AD的淀粉样蛋白级联假说，A β 42寡聚体在体内作为弥漫性斑块沉积是重要的最早期事件，导致在某些环境条件下可溶性A β的进一步积累形成纤维状淀粉样蛋白斑块。为了表征金属离子对固体表面上淀粉样蛋白沉积和斑块生长的影响，我们通过将A β低聚物固定到N-羟基琥珀酰亚胺酯活化的固体表面上来制备合成模板。根据我们的研究，使用非原位原子力显微镜（AFM），傅里叶变换红外光谱（FT-IR），和硫磺素T（ThT）荧光光谱，Cu 2+和Zn 2+离子加速A β 40和A β 42的沉积，但只导致形成“无定形”聚集体。与此相反，铁3+诱导沉积的“纤维状”淀粉样蛋白斑块在中性pH值。在弱酸性环境下，纤维状淀粉样蛋白斑块的形成没有诱导任何金属离子在这项工作中测试。使用二次离子质谱（西姆斯）分析，我们发现，结合铜离子的A β沉积物上的固体模板发生的可能减少的Cu离子的A β与Cu 2+的相互作用。我们的研究结果可能提供的作用，金属离子的纤维状或无定形淀粉样斑块的形成在AD的见解。
The abnormal deposition and aggregation of beta-amyloid (A beta) on brain tissues are considered to be one of the characteristic neuropathological features of Alzheimer's disease (AD). Environmental conditions such as metal ions, pH, and cell membranes are associated with A beta deposition and plaque formation. According to the amyloid cascade hypothesis of AD, the deposition of A beta 42 oligomers as diffuse plaques in vivo is an important earliest event, leading to the formation of fibrillar amyloid plaques by the further accumulation of soluble A beta under certain environmental conditions. In order to characterize the effect of metal ions on amyloid deposition and plaque growth on a solid surface, we prepared a synthetic template by immobilizing A beta oligomers onto a N-hydroxysuccinimide ester-activated solid surface. According to our study using ex situ atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FT-IR), and thioflavin T (ThT) fluorescence spectroscopy, Cu2+ and Zn2+ ions accelerated both A beta 40 and A beta 42 deposition but resulted only in the formation of "amorphous" aggregates. In contrast, Fe3+ induced the deposition of "fibrillar" amyloid plaques at neutral pH. Under mildly acidic environments, the formation of fibrillar amyloid plaques was not induced by any metal ion tested in this work. Using secondary ion mass spectroscopy (SIMS) analysis, we found that binding Cu ions to A beta deposits on a solid template occurred by the possible reduction of Cu ions during the interaction of A beta with Cu2+. Our results may provide insights into the role of metal ions on the formation of fibrillar or amorphous amyloid plaques in AD.