北京蛋白质组研究中心/蛋白质组学国家重点实验室钱小红研究员课题组与多国实验室合作发现亨廷顿疾病潜在生物标志物。
该研究以患者脑脊液为样本，通过6国实验室合作，规模化筛选和鉴定与亨廷顿疾病(HD)发生、发展密切相关的蛋白质。通过对基因组和蛋白质组数据的整体研究发现，人脑脊液中可检测到的在脑中高表达的蛋白（脑特异性蛋白）是血浆中的1.8倍。与正常人脑脊液相比，HD患者脑脊液中的脑特异性蛋白含量呈下调趋势，其中81%的蛋白量变与不同脑区mRNA转录水平变化一致，同时发现HD患者脑脊液中的肝相关蛋白含量上调。脑脊液中高表达的蛋白大多与免疫系统相关，这些蛋白的变化与HD特征性的神经退行性变、小神经胶质细胞增生和星形胶质细胞增生现象相吻合，提示其可作为HD的潜在生物标志物。
相关论文发表在最新一期国际蛋白质组学权威杂志：《分子与细胞蛋白质组学》（Molecular & Cellular Proteomics, MCP）上面，同期杂志还发表了该所朱云平研究员课题组、钱小红研究员课题组的两篇研究论文，创该刊单期同一单位发文数之最。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
