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绿茶和红酒中成分有望治疗遗传代谢疾病
发表日期: 2018-07-18 作者: Ehud Gazit等 文章来源:《通讯化学》
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一个国际研究团队日前发现,绿茶和红酒中的某些成分可以阻止有毒代谢物的形成,未来有望用于治疗苯丙酮尿症等遗传代谢疾病。

苯丙酮尿症是一种遗传性代谢缺陷病,患者体内特定氨基酸等无法正常代谢造成毒性淀粉样蛋白异常沉积,影响大脑及神经系统发育,导致智力严重低下。

以色列特拉维夫大学领导的一个国际研究团队在英国《通讯化学》(Communications Chemistry)杂志网络版发表论文说,他们用绿茶中的多酚类活性成分EGCG和红酒中的丹宁酸测试了苯丙酮尿症等遗传代谢疾病中的代谢物,这些代谢物与毒性淀粉样蛋白的形成有关。结果显示,EGCG和丹宁酸都能有效阻断此类蛋白的形成。

此前研究显示,上述两种成分还有助于防止一些老年疾病患者脑内的毒性淀粉样蛋白沉积,如阿尔茨海默病、帕金森病等。

研究人员表示,这项研究有助于了解代谢物在代谢性疾病、神经退行性疾病甚至癌症中的作用和重要性,未来有望开发出相关治疗方法帮助这些疾病患者。(来源:新华社)

 

Differential inhibition of metabolite amyloid formation by generic fibrillation-modifying polyphenols

 

Abstract  The formation of ordered amyloid fibrils by proteins and polypeptides is associated with human disorders. A recent extension of the amyloidogenic building block family includes several small metabolites, which form assemblies with structural and functional similarities to well-established amyloids. Here we investigate whether generic amyloid polyphenolic inhibitors can also restrict the formation of metabolite fibrils. We reveal that epigallocatechin gallate and tannic acid inhibit amyloid-like fibrillation of adenine, phenylalanine, and tyrosine. Moreover, the compounds reduce the cytotoxicity triggered by these assemblies. In contrast, acetylsalicylic acid, used as a control does not have an inhibitory effect. The compounds’ differential effects at various time points is consistent with molecular dynamics simulations, providing information about the inhibition mechanisms and inhibitors’ key interactions with the monomeric and subsequent crystalline fibril states. Taken together, we provide additional evidence for the fundamental similarities between protein- and metabolite-based amyloids, the inhibition process and dynamics of association.

 

原文链接:https://www.nature.com/articles/s42004-018-0025-z.pdf

 


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