Curcuminoid Binds to Amyloid-β1-42 Oligomer and Fibril
Curcuminoid Binds to Amyloid-β1-42 Oligomer and Fibril
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DOI：
10.3233/jad-2011-102100
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发表时间：
2011-01-01
影响因子：
4
通讯作者：
Tooyama, Ikuo
中科院分区：
文献类型：
--
作者：
Yanagisawa, Daijiro;Taguchi, Hiroyasu;Tooyama, Ikuo
阿尔茨海默病（AD）的研究强烈支持淀粉样蛋白β（A β）在脑中的沉积是AD进展的起始事件的假设。A β肽很容易形成长的不溶性淀粉样纤维，积累在称为老年斑的沉积物中。另一方面，最近的研究表明，可溶性A β寡聚体，而不是单体或不溶性A β原纤维，可能是AD中神经元和突触功能障碍的原因。姜黄素是一种来源于姜黄植物的低分子量黄橙色色素，已在AD转基因小鼠模型中显示出治疗效果。然而，目前尚不清楚姜黄素是否直接与A β寡聚体相互作用。本研究调查了姜黄素和A β低聚物（如球聚物和A β衍生的可扩散配体（ADDL））之间的任何相互作用。通过电子显微镜分析观察到球聚物为球形结构簇，并且还检测到ADDL为小球形结构。荧光分析显示，姜黄素的荧光显着增加时，与两个低聚物反应。此外，石英晶体微天平分析表明，在低聚物固定化电极的频率显着下降后，姜黄素。这些结果有力地表明姜黄素与A β寡聚体和A β原纤维结合。姜黄素与A β寡聚体的结合可能有助于对AD的治疗作用。基于这些发现，姜黄素可以为靶向A β寡聚体的AD疗法提供新概念的基础。
Studies of Alzheimer's disease (AD) strongly support the hypothesis that amyloid-beta (A beta) deposition in the brain is the initiating event in the progression of AD. A beta peptides easily form long insoluble amyloid fibrils, which accumulate in deposits known as senile plaques. On the other hand, recent work indicated that soluble A beta oligomers, rather than monomers or insoluble A beta fibrils, might be responsible for neuronal and synaptic dysfunction in AD. Curcumin, a low molecular weight yellow-orange pigment derived from the turmeric plant, has shown therapeutic effects in transgenic mouse models of AD. However, it remains unclear whether curcumin interacts directly with the A beta oligomers. This study investigated any interaction between curcumin and A beta oligomers such as globulomer and A beta-derived diffusible ligand (ADDL). Globulomer was observed as a cluster of spherical structures by electron microscopic analysis, and ADDL was also detected as small spherical structures. Fluorescence analysis revealed a significant increase in the fluorescence of curcumin when reacted with both oligomers. Furthermore quartz crystal microbalance analysis showed significant frequency decreases in oligomer-immobilized electrodes following the addition of curcumin. These results strongly suggested that curcumin binds to A beta oligomers and to A beta fibrils. The association of curcumin with A beta oligomers may contribute to the therapeutic effect on AD. Based on these findings, curcumin could provide the basis of a novel concept in AD therapies targeting A beta oligomers.