Binding of epigallocatechin-3-gallate to transthyretin modulates its amyloidogenicity
Binding of epigallocatechin-3-gallate to transthyretin modulates its amyloidogenicity
复制标题
DOI：
10.1016/j.febslet.2009.10.062
复制
发表时间：
2009-11-19
期刊：
影响因子：
3.5
通讯作者：
Almeida, Maria Rosario
中科院分区：
文献类型：
--
作者：
Ferreira, Nelson;Cardoso, Isabel;Almeida, Maria Rosario
超过100种甲状腺素运载蛋白（TTR）变异与遗传性淀粉样变性有关。干扰导致原纤维形成的事件级联的任何步骤的TTR淀粉样变性的方法具有治疗潜力。在这项研究中，我们测试了（-）-表没食子儿茶素-3-没食子酸酯（EGCG），最丰富的儿茶素的绿色茶，作为TTR淀粉样蛋白形成的抑制剂。我们证明，表没食子儿茶素没食子酸酯结合TTR“在体外”和“离体”，并抑制TTR聚集“在体外”，并在细胞培养系统。这些发现与化合物的低毒性一起提高了在家族性淀粉样多发性神经病的治疗方法中使用EGCG的可能性，家族性淀粉样多发性神经病是遗传性TTR淀粉样变性的最常见形式。结构化概要：MINT-7294529：TTR（uniprotkb：P02766）和TTR（uniprotkb：P02766）通过在非变性凝胶电泳中共迁移结合（MI：0407）（C）2009欧洲生物化学学会联合会。由Elsevier B出版。V.保留所有权利。
More than 100 transthyretin (TTR) variants are associated with hereditary amyloidosis. Approaches for TTR amyloidosis that interfere with any step of the cascade of events leading to fibril formation have therapeutic potential. In this study we tested (-)-epigallocatechin-3-gallate (EGCG), the most abundant catechin of green tea, as an inhibitor of TTR amyloid formation. We demonstrate that EGCG binds to TTR "in vitro" and "ex vivo" and that EGCG inhibits TTR aggregation "in vitro" and in a cell culture system. These findings together with the low toxicity of the compound raise the possibility of using EGCG in a therapeutic approach for familial amyloidotic polyneuropathy, the most frequent form of hereditary TTR amyloidosis.Structured summary:MINT-7294529: TTR (uniprotkb:P02766) and TTR (uniprotkb:P02766) bind (MI:0407) by comigration in non-denaturing gel electrophoresis (MI:0404) (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.