来源
生命经纬
2006-10-20 9:53:17
<<Molecular Cell>>：揭示MicroRNA参与调节神经衰退疾病
10月6日的国际权威杂志Molecular Cell上，来自宾夕法尼亚州大学生物系的研究人员发表了一篇MicroRNA研究的新发现。他们发现MicroRNA途径能够调节多聚谷氨酰胺诱导的神经退化作用。值得一提的是，文章第二作者是华裔研究人员刘楠（Nan Liu）。
有九种神经衰退疾病(neurodegenerative disease)是由于基因的开发阅读框中一种CAG重复编码谷胺酸的扩增造成的。多聚谷氨酰胺（Polyglutamine；polyQ）序列产生了显性的的毒性，从而导致神经元的退化。在这项新的研究中，为了弄清miRNA途径是否在神经退化过程中起到一定的作用，研究人员分析了对miRNA加工过程很关键的基因如何调节由III型脊髓小脑性共济失调（spinocerebellar ataxia）蛋白诱导的毒性。
研究表明，果蝇和人类细胞中miRNA加工过程的减少使polyQ毒性明显增加。在基因筛选过程中，研究人员确定出miRNA bantam是果蝇中多聚谷氨酰胺（polyQ）和tau毒性的一个强大的调节因子。新的研究揭示出ban在SCA3蛋白的下游起功能，从而抑制退化的发生。这些发现意味着miRNA途径能显著调节polyQ和tau诱导的神经退化作用，进而为研发治疗这类基本的药物奠定基础。
参考文献：
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.
