Curcumin has potent anti-amyloidogenic effects for Alzheimer's β-amyloid fibrils in vitro
Curcumin has potent anti-amyloidogenic effects for Alzheimer's β-amyloid fibrils in vitro
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DOI：
10.1002/jnr.20025
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发表时间：
2004-03-15
影响因子：
4.2
通讯作者：
Yamada, M
中科院分区：
文献类型：
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作者：
Ono, K;Hasegawa, K;Yamada, M
抑制淀粉样β-肽（Abeta）的积累和由Abeta形成β-淀粉样纤维（fAbeta），以及预先形成的fAbeta在中枢神经系统中的去稳定化，将是治疗阿尔茨海默病（AD）的有吸引力的治疗靶点。我们先前报道了去甲二氢愈创木酸（NDGA）和葡萄酒相关多酚在体外剂量依赖性地抑制Abeta（1-40）和Abeta（1-42）形成fAbeta，并使预先形成的fAbeta（1-40）和fAbeta（1-42）不稳定。利用荧光光谱分析和电子显微镜研究，我们研究了姜黄素（Cur）和迷迭香酸（RA）在体外pH 7.5和37 ℃下对fAbeta（1-40）和fAbeta（1-42）的形成，延伸和去稳定化的影响。我们接下来比较了Cur和RA与NDGA的抗淀粉样蛋白生成活性。Cur和RA剂量依赖性地抑制Abeta（1-40）和Abeta（1-42）的fAbeta形成以及它们的延伸。此外，它们剂量依赖性地使预先形成的fAbeta不稳定。Cur、RA和NDGA的总体活性相似。Cur、RA和NDGA对fAbetas的形成、延伸和去稳定化的有效浓度（EC 50）在0.1-1 μ M的量级。尽管Cur和RA抑制Abeta形成fAbeta并在体外使预先形成的fAbeta不稳定的机制仍不清楚，但它们可能是开发AD治疗剂的关键分子。(C)2004 Wiley-Liss，Inc.
Inhibition of the accumulation of amyloid beta-peptide (Abeta) and the formation of beta-amyloid fibrils (fAbeta) from Abeta, as well as the destabilization of preformed fAbeta in the central nervous system, would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). We reported previously that nordihydroguaiaretic acid (NDGA) and wine-related polyphenols inhibit fAbeta formation from Abeta(1-40) and Abeta(1-42) and destabilize preformed fAbeta(1-40) and fAbeta(1-42) dose-dependently in vitro. Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of curcumin (Cur) and rosmarinic acid (RA) on the formation, extension, and destabilization of fAbeta(1-40) and fAbeta(1-42) at pH 7.5 at 37degreesC in vitro. We next compared the anti-amyloidogenic activities of Cur and RA with NDGA. Cur and RA dose-dependently inhibited fAbeta formation from Abeta(1-40) and Abeta(1-42), as well as their extension. In addition, they dose-dependently destabilized preformed fAbetas. The overall activities of Cur, RA, and NDGA were similar. The effective concentrations (EC50) of Cur, RA, and NDGA for the formation, extension, and destabilization of fAbetas were in the order of 0.1-1 muM. Although the mechanism by which Cur and RA inhibit fAbeta formation from Abeta and destabilize preformed fAbeta in vitro remains unclear, they could be a key molecule for the development of therapeutics for AD. (C) 2004 Wiley-Liss, Inc.