Resveratrol inhibits beta-amyloid oligomeric cytotoxicity but does not prevent oligomer formation
Resveratrol inhibits beta-amyloid oligomeric cytotoxicity but does not prevent oligomer formation
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DOI：
10.1016/j.neuro.2009.08.013
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发表时间：
2009-11-01
期刊：
影响因子：
3.4
通讯作者：
Liu, Rui-tian
中科院分区：
文献类型：
--
作者：
Feng, Ying;Wang, Xiao-ping;Liu, Rui-tian
β-淀粉样蛋白（A β）聚集与神经退行性病变和阿尔茨海默病（AD）的一系列有害事件密切相关。抑制A β组装、使预先形成的A β聚集体不稳定以及减弱A β寡聚体和原纤维的细胞毒性可能是AD患者的有价值的治疗方法。最近的研究表明，适量饮用红葡萄酒和摄入膳食多酚，如白藜芦醇，可能有利于动物模型中的AD表型，并降低AD临床痴呆的相对风险。为了了解这种神经保护作用的机制，我们研究了白藜芦醇（葡萄酒和许多植物中多酚的活性成分）对A β 42单体聚合、A β 42原纤维不稳定和A β 42体外细胞毒性的影响，使用硫磺素T（ThT）荧光光谱分析、透射电子显微镜（TEM）、圆二色性（CD）和MTT测定。结果表明，白藜芦醇可剂量依赖性地抑制A β 42纤维形成和细胞毒性，但不能阻止A β 42寡聚化。Western-blot、Dot-blot和ELISA研究证实，白藜芦醇的加入导致大量A β 42寡聚体的形成。结合A β寡聚体与A β毒性相关的概念，我们推测，除了潜在的抗氧化活性外，白藜芦醇可能直接与A β 42结合，干扰A β 42聚集，改变A β 42寡聚体构象并减弱A β 42寡聚体细胞毒性。(C)2009 Elsevier Inc. All rights reserved.
Beta-amyloid (A beta) aggregation has been strongly associated with the neurodegenerative pathology and a cascade of harmful event rated to Alzheimer's disease (AD). Inhibition of A beta assembly, destabilization of preformed A beta aggregates and attenuation of the cytotoxicity of A beta oligomers and fibrils could be valuable therapeutics of patients with AD. Recent studies suggested that moderate consumption of red wine and intake of dietary polyphenols, such as resveratrol, may benefit AD phenotypes in animal models and reduce the relative risk for AD clinical dementia. To understand the mechanism of this neuroprotection, we studied the effects of resveratrol, an active ingredient of polyphenols in wine and many plants, on the polymerization of A beta 42 monomer, the destabilization of A beta 42 fibril and the cell toxicity of A beta 42 in vitro using fluorescence spectroscopic analysis with thioflavin T (ThT), transmission electron microscope (TEM), circular dichroism (CD) and MTT assay. The results showed that resveratrol could dose-dependently inhibit A beta 42 fibril formation and cytotoxicity but could not prevent A beta 42 oligomerization. The studies by Western-blot, dot-blot and ELISA confirmed that the addition of resveratrol resulted in numerous A beta 42 oligomer formation. In conjunction with the concept that A beta oligomers are linked to A beta toxicity, we speculate that aside from potential antioxidant activities, resveratrol may directly bind to A beta 42, interfere in A beta 42 aggregation, change the A beta 42 oligomer conformation and attenuate A beta 42 oligomeric cytotoxicity. (C) 2009 Elsevier Inc. All rights reserved.