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酚类化合物对转基因秀丽隐杆线虫中 Aβ 聚集和 Aβ 诱导毒性的影响。

Effect of phenolic compounds against Aβ aggregation and Aβ-induced toxicity in transgenic C. elegans.

机构信息

Bioorganic Laboratory, Central Leather Research Institute (CSIR), Adyar, Chennai 600 020, India.

出版信息

Neurochem Res. 2012 Jan;37(1):40-8. doi: 10.1007/s11064-011-0580-5. Epub 2011 Aug 21.

Abstract

Substantial evidence suggests that the aggregation of amyloid-β (Aβ) peptide into fibrillar structures that is rich in β-sheets is implicated as the cause of Alzheimer's disease. Therefore, an attractive therapeutic strategy is to prevent or alter Aβ aggregation. Phenolic compounds are natural substances that are composed of one or more aromatic phenolic rings and present in wine, tea, fruits, vegetables and a wide variety of plants. In this work, we investigated the effects of ferulic acid, morin, quercetin and gossypol against Aβ aggregation. From the ThT and turbidity assays, it is observed that in addition to the fibril aggregate, another type of aggregate is formed in the presence of morin, quercetin, and gossypol. On the other hand, ferulic acid did not prevent fibril formation, but it did appear to reduce the average length of fibrils compared to Aβ alone. To study the protective effects of phenolic compounds on Aβ-induced toxicity, we utilized the nematode Caenorhabditis elegans (C. elegans) as an in vivo model organism, human Aβ is expressed intracellularly in the body wall muscle. We found that exposure of Caenorhabditis elegans to ferulic acid give more protection against Aβ toxicity than morin, quercetin and gossypol.

摘要

大量证据表明,淀粉样蛋白-β (Aβ) 肽聚集形成富含 β-折叠的纤维状结构与阿尔茨海默病的发生有关。因此,一种有吸引力的治疗策略是预防或改变 Aβ 聚集。酚类化合物是天然物质,由一个或多个芳香酚环组成,存在于葡萄酒、茶、水果、蔬菜和各种植物中。在这项工作中,我们研究了阿魏酸、桑色素、槲皮素和棉酚对 Aβ 聚集的影响。从 ThT 和浊度测定中可以看出,除了纤维状聚集体之外,在桑色素、槲皮素和棉酚的存在下还形成了另一种类型的聚集体。另一方面,阿魏酸并没有阻止纤维的形成,但它似乎确实减少了与单独的 Aβ 相比纤维的平均长度。为了研究酚类化合物对 Aβ 诱导的毒性的保护作用,我们利用秀丽隐杆线虫 (C. elegans) 作为体内模型生物,在体壁肌肉中表达人 Aβ。我们发现,暴露于阿魏酸中的秀丽隐杆线虫比桑色素、槲皮素和棉酚对 Aβ 毒性的保护作用更强。

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