科學(xué)家們發(fā)明了一種全新方法,，可以瓦解神經(jīng)退化性疾病患者大腦中不正常堆積的蛋白質(zhì),，新成果發(fā)表在7月在線出版的《自然—化學(xué)生物學(xué)》期刊上。
神經(jīng)退化性疾病,，如阿爾茨海默氏癥,、亨廷頓氏癥和帕金森氏癥等，其特點(diǎn)是蛋白質(zhì)在大腦中的毒性堆積,。這些堆積源于蛋白質(zhì)之間的非正常相互作用,，它們不僅在視覺上是可見的，而且阻斷了其他有重要細(xì)胞功能的蛋白質(zhì)的自然流動,。在以前的研究中,，研究人員用小分子或酶阻斷這些蛋白質(zhì)的堆積，改善了病情,。環(huán)肽則是另一種選擇,，因為它們能影響蛋白質(zhì)間的相互作用，在神經(jīng)退化性疾病中,，這些蛋白質(zhì)間的相互作用出了故障,。
Susan Lindquist和同事研究了出現(xiàn)蛋白質(zhì)堆積和神經(jīng)退化性疾病癥狀的模式動物酵母。他們鑒別出可緩解酵母蛋白質(zhì)堆積的幾個環(huán)肽,。這些環(huán)肽也救助了神經(jīng)退化性疾病模型線蟲的神經(jīng)細(xì)胞,。新方法可用于研究神經(jīng)退化性疾病的機(jī)理，也有助于研制新的治療方法,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
