淀粉纖維是一種毒性蛋白質(zhì),，它的堆積與阿爾茨海默氏癥和帕金森氏癥有關(guān),。一項(xiàng)新研究發(fā)現(xiàn)，綠茶提取物兒茶素（EGCG）可以預(yù)防淀粉纖維的形成,。新結(jié)果在線發(fā)表在6月號的《自然—結(jié)構(gòu)與分子生物學(xué)》（Nature Structural & Molecular Biology）期刊上,，它為設(shè)計更有效防止淀粉狀蛋白質(zhì)形成的化合物指出一種新方法，這類蛋白質(zhì)與神經(jīng)退化性疾病的發(fā)生密切相關(guān),。
研究人員早已發(fā)現(xiàn)淀粉纖維在阿爾茨海默氏癥和帕金森氏癥患者體內(nèi)的堆積,，他們認(rèn)為，這是某種開放式蛋白質(zhì)的錯誤折疊或堆積造成的,，這種堆積會毒害細(xì)胞并導(dǎo)致神經(jīng)功能的退化,。 Erich Wanker和同事發(fā)現(xiàn)，綠茶中的兒茶素能與這些天然的開放式蛋白質(zhì)結(jié)合在一起,，防止它們轉(zhuǎn)化成有毒的蛋白質(zhì),。而且，EGCG還能指導(dǎo)這些蛋白質(zhì)“遠(yuǎn)離”堆積的途徑,，成為對細(xì)胞無害的蛋白質(zhì),。
作者發(fā)現(xiàn)，EGCG還能與其他與這些疾病無關(guān)的開放式蛋白質(zhì)結(jié)合,，因此,，下一步的工作將直接設(shè)計新化合物，讓它們能選擇性識別與淀粉纖維形成有關(guān)的蛋白質(zhì),。（生物谷Bioon.com）
生物谷推薦原始出處：
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
AbstractThe 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.
