科学家们发明了一种全新方法，可以瓦解神经退化性疾病患者大脑中不正常堆积的蛋白质，新成果发表在7月在线出版的《自然—化学生物学》期刊上。
神经退化性疾病，如阿尔茨海默氏症、亨廷顿氏症和帕金森氏症等，其特点是蛋白质在大脑中的毒性堆积。这些堆积源于蛋白质之间的非正常相互作用，它们不仅在视觉上是可见的，而且阻断了其他有重要细胞功能的蛋白质的自然流动。在以前的研究中，研究人员用小分子或酶阻断这些蛋白质的堆积，改善了病情。环肽则是另一种选择，因为它们能影响蛋白质间的相互作用，在神经退化性疾病中，这些蛋白质间的相互作用出了故障。
Susan Lindquist和同事研究了出现蛋白质堆积和神经退化性疾病症状的模式动物酵母。他们鉴别出可缓解酵母蛋白质堆积的几个环肽。这些环肽也救助了神经退化性疾病模型线虫的神经细胞。新方法可用于研究神经退化性疾病的机理，也有助于研制新的治疗方法。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature Chemical Biology 13 July 2009 | doi:10.1038/nchembio.193
Rapid selection of cyclic peptides that reduce -synuclein toxicity in yeast and animal models
Joshua A Kritzer1, Shusei Hamamichi2, J Michael McCaffery3, Sandro Santagata1,4, Todd A Naumann5, Kim A Caldwell2, Guy A Caldwell2 & Susan Lindquist1,6
Phage display has demonstrated the utility of cyclic peptides as general protein ligands but cannot access proteins inside eukaryotic cells. Expanding a new chemical genetics tool, we describe the first expressed library of head-to-tail cyclic peptides in yeast (Saccharomyces cerevisiae). We applied the library to selections in a yeast model of -synuclein toxicity that recapitulates much of the cellular pathology of Parkinson's disease. From a pool of 5 million transformants, we isolated two related cyclic peptide constructs that specifically reduced the toxicity of human -synuclein. These expressed cyclic peptide constructs also prevented dopaminergic neuron loss in an established Caenorhabditis elegans Parkinson's model. This work highlights the speed and efficiency of using libraries of expressed cyclic peptides for forward chemical genetics in cellular models of human disease.
1 Whitehead Institute for Biomedical Research, Cambridge Massachusetts, USA.
2 Department of Biological Sciences, University of Alabama, Tuscaloosa, Alabama, USA.
3 Integrated Imaging Center and Department of Biology, Johns Hopkins University, Baltimore, Maryland, USA.
4 Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
5 Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania, USA.
6 Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge Massachusetts, USA.
