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绿茶提取物可预防淀粉纤维形成

来源:科学时报 2008-09-03 14:45

淀粉纤维是一种毒性蛋白质,它的堆积与阿尔茨海默氏症和帕金森氏症有关。一项新研究发现,绿茶提取物儿茶素(EGCG)可以预防淀粉纤维的形成。新结果在线发表在6月号的《自然—结构与分子生物学》(Nature Structural & Molecular Biology)期刊上,它为设计更有效防止淀粉状蛋白质形成的化合物指出一种新方法,这类蛋白质与神经退化性疾病的发生密切相关。

研究人员早已发现淀粉纤维在阿尔茨海默氏症和帕金森氏症患者体内的堆积,他们认为,这是某种开放式蛋白质的错误折叠或堆积造成的,这种堆积会毒害细胞并导致神经功能的退化。 Erich Wanker和同事发现,绿茶中的儿茶素能与这些天然的开放式蛋白质结合在一起,防止它们转化成有毒的蛋白质。而且,EGCG还能指导这些蛋白质“远离”堆积的途径,成为对细胞无害的蛋白质。

作者发现,EGCG还能与其他与这些疾病无关的开放式蛋白质结合,因此,下一步的工作将直接设计新化合物,让它们能选择性识别与淀粉纤维形成有关的蛋白质。(生物谷Bioon.com)

生物谷推荐原始出处:

Nature Structural & Molecular Biology,Dagmar E Ehrnhoefer,Erich E Wanker

EGCG redirects amyloidogenic polypeptides into unstructured, off-pathway oligomers

Dagmar E Ehrnhoefer1,4, Jan Bieschke1,4, Annett Boeddrich1, Martin Herbst1, Laura Masino2, Rudi Lurz3, Sabine Engemann1, Annalisa Pastore2 & Erich E Wanker1

The accumulation of β-sheet–rich amyloid fibrils or aggregates is a complex, multistep process that is associated with cellular toxicity in a number of human protein misfolding disorders, including Parkinson's and Alzheimer's diseases. It involves the formation of various transient and intransient, on- and off-pathway aggregate species, whose structure, size and cellular toxicity are largely unclear. Here we demonstrate redirection of amyloid fibril formation through the action of a small molecule, resulting in off-pathway, highly stable oligomers. The polyphenol (- )-epigallocatechin gallate efficiently inhibits the fibrillogenesis of both α-synuclein and amyloid-β by directly binding to the natively unfolded polypeptides and preventing their conversion into toxic, on-pathway aggregation intermediates. Instead of β-sheet–rich amyloid, the formation of unstructured, nontoxic α-synuclein and amyloid-β oligomers of a new type is promoted, suggesting a generic effect on aggregation pathways in neurodegenerative diseases.

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