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芪类化合物对阿尔茨海默病β-淀粉样蛋白原纤维的体外抑制活性。

Inhibitory activity of stilbenes on Alzheimer's beta-amyloid fibrils in vitro.

作者信息

Rivière Céline, Richard Tristan, Quentin Lysiane, Krisa Stéphanie, Mérillon Jean-Michel, Monti Jean-Pierre

机构信息

Laboratoire de physique et biophysique, Université de Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux cedex, France.

出版信息

Bioorg Med Chem. 2007 Jan 15;15(2):1160-7. doi: 10.1016/j.bmc.2006.09.069. Epub 2006 Oct 1.

Abstract

Polymerization of the amyloid beta-peptide (Abeta) has been identified as one of the major characteristics of Alzheimer's disease (AD). Thus, finding molecules to prevent the aggregation of Abeta could be of therapeutic value in AD. We describe an original routine in vitro assay to search for inhibitors of Abeta(25-35) fibril formation which uses UV-visible measurements and electron microscopy (EM). In particular, this routine assay was used to examine the effects of stilbenes, a well-known polyphenol class, as inhibitors of Abeta fibril formation. The inhibitory properties of resveratrol (RES), piceid (PIC), resveratrol diglucoside (DIG), piceatannol (PIA), astringine (AST), and viniferin (VIN) were characterized and compared. RES and PIC effectively and dose-dependently inhibited Abeta polymerization while other polyphenols exerted less inhibition. Although the mechanism of anti-amyloidogenic activity is still unknown, these results support the hypothesis that stilbenes could be of therapeutic value in AD.

摘要

淀粉样β肽(Aβ)的聚合已被确定为阿尔茨海默病(AD)的主要特征之一。因此,寻找能够阻止Aβ聚集的分子可能对AD具有治疗价值。我们描述了一种原始的体外常规检测方法,用于寻找Aβ(25-35)纤维形成的抑制剂,该方法使用紫外可见测量和电子显微镜(EM)。特别地,该常规检测用于研究著名的多酚类——芪类作为Aβ纤维形成抑制剂的作用。对白藜芦醇(RES)、白藜芦醇糖苷(PIC)、白藜芦醇二糖苷(DIG)、紫铆因(PIA)、阿斯汀(AST)和葡萄素(VIN)的抑制特性进行了表征和比较。RES和PIC有效且剂量依赖性地抑制Aβ聚合,而其他多酚的抑制作用较小。尽管抗淀粉样生成活性的机制仍然未知,但这些结果支持芪类可能对AD具有治疗价值这一假说。

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