Preformed β-amyloid fibrils are destabilized by coenzyme Q10 in vitro
Preformed β-amyloid fibrils are destabilized by coenzyme Q10 in vitro
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DOI：
10.1016/j.bbrc.2005.02.132
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发表时间：
2005-04-29
影响因子：
3.1
通讯作者：
Yamada, M
中科院分区：
文献类型：
--
作者：
Ono, K;Hasegawa, K;Yamada, M
抑制β-淀粉样蛋白原纤维（fA β）的形成以及使CNS中预先形成的fA β不稳定将是治疗阿尔茨海默病（AD）的有吸引力的治疗靶点。我们以前报道过，去甲二氢愈创木酸（NDGA）和葡萄酒相关的多酚，杨梅素（Myr），抑制fA β形成从A β和不稳定的预制fA β在体外。使用荧光光谱分析与硫磺素T和电子显微镜研究，我们研究了辅酶Q（10）（辅酶Q（10））的形成，扩展和fA β在体外pH值7.5，37 ℃不稳定的影响。我们接下来比较了辅酶Q（10）与NDGA和Myr的抗淀粉样蛋白生成活性。辅酶Q（10）剂量依赖性地抑制淀粉样β肽（A β）形成fA β，以及它们的延伸。此外，它使预先形成的fA β不稳定。CoQ（10）的抗淀粉样蛋白生成作用略弱于NDGA和Myr。辅酶Q（10）可能是开发AD治疗药物的关键分子。(c)2005年爱思唯尔公司All rights reserved.
Inhibition of the formation of beta-amyloid fibrils (fA beta), as well as the destabilization of preformed fA beta in the CNS, would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). We reported previously that nordihydroguaiaretic acid (NDGA) and wine-related polyphenol, myricetin (Myr), inhibit fA beta formation from A beta and destabilize preformed fA beta in vitro. Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of coenzyme Q(10) (CoQ(10)) on the formation, extension, and destabilization of fA beta at pH 7.5 at 37 degrees C in vitro. We next compared the anti-amyloidogenic activities of CoQ(10) with NDGA and Myr. CoQ(10) dose-dependently inhibited fA beta formation from amyloid beta-peptide (A beta), as well as their extension. Moreover, it destabilized preformed fA beta s. The anti-amyloidogenic effects of CoQ(10) were slightly weaker than those of NDGA and Myr. CoQ(10) could be a key molecule for the development of therapeutics for AD. (c) 2005 Elsevier Inc. All rights reserved.