10月6日的國際權(quán)威雜志Molecular Cell上,，來自賓夕法尼亞州大學(xué)生物系的研究人員發(fā)表了一篇MicroRNA研究的新發(fā)現(xiàn),。他們發(fā)現(xiàn)MicroRNA途徑能夠調(diào)節(jié)多聚谷氨酰胺誘導(dǎo)的神經(jīng)退化作用,。值得一提的是,，文章第二作者是華裔研究人員劉楠（Nan Liu）,。
有九種神經(jīng)衰退疾病(neurodegenerative disease)是由于基因的開發(fā)閱讀框中一種CAG重復(fù)編碼谷胺酸的擴(kuò)增造成的,。多聚谷氨酰胺（Polyglutamine,；polyQ）序列產(chǎn)生了顯性的的毒性,，從而導(dǎo)致神經(jīng)元的退化,。在這項(xiàng)新的研究中，為了弄清miRNA途徑是否在神經(jīng)退化過程中起到一定的作用,，研究人員分析了對miRNA加工過程很關(guān)鍵的基因如何調(diào)節(jié)由III型脊髓小腦性共濟(jì)失調(diào)（spinocerebellar ataxia）蛋白誘導(dǎo)的毒性,。
研究表明，果蠅和人類細(xì)胞中miRNA加工過程的減少使polyQ毒性明顯增加,。在基因篩選過程中,，研究人員確定出miRNA bantam是果蠅中多聚谷氨酰胺（polyQ）和tau毒性的一個強(qiáng)大的調(diào)節(jié)因子。新的研究揭示出ban在SCA3蛋白的下游起功能,，從而抑制退化的發(fā)生,。這些發(fā)現(xiàn)意味著miRNA途徑能顯著調(diào)節(jié)polyQ和tau誘導(dǎo)的神經(jīng)退化作用，進(jìn)而為研發(fā)治療這類基本的藥物奠定基礎(chǔ),。
參考文獻(xiàn)：
MicroRNA Pathways Modulate Polyglutamine-Induced Neurodegeneration Molecular Cell,，Volume 24, Issue 1, 6 October 2006, Pages 157-163
Julide Bilen, Nan Liu, Barrington G. Burnett, Randall N. Pittman and Nancy M. Bonini
部分英文原文：
MicroRNA Pathways Modulate Polyglutamine-Induced Neurodegeneration
Nine human neurodegenerative diseases are due to expansion of a CAG repeat- encoding glutamine within the open reading frame of the respective genes. Polyglutamine (polyQ) expansion confers dominant toxicity, resulting in neuronal degeneration. MicroRNAs (miRNAs) have been shown to modulate programmed cell death during development. To address whether miRNA pathways play a role in neurodegeneration, we tested whether genes critical for miRNA processing modulated toxicity induced by the spinocerebellar ataxia type 3 (SCA3) protein. These studies revealed a striking enhancement of polyQ toxicity upon reduction of miRNA processing in Drosophila and human cells. In parallel genetic screens, we identified the miRNA bantam (ban) as a potent modulator of both polyQ and tau toxicity in flies. Our studies suggest that ban functions downstream of toxicity of the SCA3 protein, to prevent degeneration. These findings indicate that miRNA pathways dramatically modulate polyQ- and tau-induced neurodegeneration, providing the foundation for new insight into therapeutics.
