北京蛋白質(zhì)組研究中心/蛋白質(zhì)組學國家重點實驗室錢小紅研究員課題組與多國實驗室合作發(fā)現(xiàn)亨廷頓疾病潛在生物標志物,。
該研究以患者腦脊液為樣本,，通過6國實驗室合作，規(guī)?；Y選和鑒定與亨廷頓疾病(HD)發(fā)生,、發(fā)展密切相關的蛋白質(zhì)。通過對基因組和蛋白質(zhì)組數(shù)據(jù)的整體研究發(fā)現(xiàn),，人腦脊液中可檢測到的在腦中高表達的蛋白（腦特異性蛋白）是血漿中的1.8倍,。與正常人腦脊液相比，HD患者腦脊液中的腦特異性蛋白含量呈下調(diào)趨勢,，其中81%的蛋白量變與不同腦區(qū)mRNA轉(zhuǎn)錄水平變化一致,，同時發(fā)現(xiàn)HD患者腦脊液中的肝相關蛋白含量上調(diào)。腦脊液中高表達的蛋白大多與免疫系統(tǒng)相關,，這些蛋白的變化與HD特征性的神經(jīng)退行性變,、小神經(jīng)膠質(zhì)細胞增生和星形膠質(zhì)細胞增生現(xiàn)象相吻合,，提示其可作為HD的潛在生物標志物。
相關論文發(fā)表在最新一期國際蛋白質(zhì)組學權(quán)威雜志：《分子與細胞蛋白質(zhì)組學》（Molecular & Cellular Proteomics, MCP）上面,，同期雜志還發(fā)表了該所朱云平研究員課題組,、錢小紅研究員課題組的兩篇研究論文，創(chuàng)該刊單期同一單位發(fā)文數(shù)之最,。（生物谷Bioon.com）
生物谷推薦原始出處：
Molecular & Cellular Proteomics 8:451-466, 2009.doi:10.1074/mcp.M800231-MCP200
Brain-specific Proteins Decline in the Cerebrospinal Fluid of Humans with Huntington Disease
Qiaojun Fang, Andrew Strand, Wendy Law, Vitor M. Faca, Matthew P. Fitzgibbon, Nathalie Hamel?, Benoit Houle?, Xin Liu||, Damon H. May, Gereon Poschmann**, Line Roy?, Kai Stühler**, Wantao Ying||, Jiyang Zhang||, Zhaobin Zheng||, John J. M. Bergeron?, Sam Hanash, Fuchu He||, Blair R. Leavitt, Helmut E. Meyer**, Xiaohong Qian|| and Martin W. McIntosh,
From the Public Health Sciences Division and Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, ? Department of Anatomy and Cell Biology, McGill University, Quebec H3A 1A4, Canada, || State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing 102206, China, ** Medizinisches Proteom-Center, Ruhr-Universit?t Bochum, D-447801 Bochum, Germany, and Department of Medical Genetics, University of British Columbia and Center for Molecular Medicine and Therapeutics, Child and Family Research Institute, Vancouver, British Columbia V5Z 4H4, Canada
We integrated five sets of proteomics data profiling the constituents of cerebrospinal fluid (CSF) derived from Huntington disease (HD)-affected and -unaffected individuals with genomics data profiling various human and mouse tissues, including the human HD brain. Based on an integrated analysis, we found that brain-specific proteins are 1.8 times more likely to be observed in CSF than in plasma, that brain-specific proteins tend to decrease in HD CSF compared with unaffected CSF, and that 81% of brain-specific proteins have quantitative changes concordant with transcriptional changes identified in different regions of HD brain. The proteins found to increase in HD CSF tend to be liver-associated. These protein changes are consistent with neurodegeneration, microgliosis, and astrocytosis known to occur in HD. We also discuss concordance between laboratories and find that ratios of individual proteins can vary greatly, but the overall trends with respect to brain or liver specificity were consistent. Concordance is highest between the two laboratories observing the largest numbers of proteins.
