Department of Pathology, University of Washington, Seattle, WA 98104, USA.
Mass Spectrom Rev. 2010 Jan-Feb;29(1):79-125. doi: 10.1002/mas.20221.
Protein glycosylation regulates protein function and cellular distribution. Additionally, aberrant protein glycosylations have been recognized to play major roles in human disorders, including neurodegenerative diseases. Glycoproteomics, a branch of proteomics that catalogs and quantifies glycoproteins, provides a powerful means to systematically profile the glycopeptides or glycoproteins of a complex mixture that are highly enriched in body fluids, and therefore, carry great potential to be diagnostic and/or prognostic markers. Application of this mass spectrometry-based technology to the study of neurodegenerative disorders (e.g., Alzheimer's disease and Parkinson's disease) is relatively new, and is expected to provide insight into the biochemical pathogenesis of neurodegeneration, as well as biomarker discovery. In this review, we have summarized the current understanding of glycoproteins in biology and neurodegenerative disease, and have discussed existing proteomic technologies that are utilized to characterize glycoproteins. Some of the ongoing studies, where glycoproteins isolated from cerebrospinal fluid and human brain are being characterized in Parkinson's disease at different stages versus controls, are presented, along with future applications of targeted validation of brain specific glycoproteins in body fluids.
蛋白质糖基化调节蛋白质功能和细胞分布。此外，异常的蛋白质糖基化已被认为在人类疾病中起主要作用，包括神经退行性疾病。糖蛋白质组学是蛋白质组学的一个分支，它对糖蛋白进行分类和定量，为系统地分析体液中高度富集的复杂混合物中的糖肽或糖蛋白提供了有力手段，因此具有作为诊断和/或预后标志物的巨大潜力。这种基于质谱的技术在神经退行性疾病（如阿尔茨海默病和帕金森病）研究中的应用相对较新，有望深入了解神经退行性变的生化发病机制以及生物标志物的发现。在这篇综述中，我们总结了糖蛋白在生物学和神经退行性疾病中的现有认识，并讨论了用于糖蛋白表征的现有蛋白质组学技术。介绍了一些正在进行的研究，即从不同阶段的帕金森病患者和对照组的脑脊液和人脑分离的糖蛋白进行特征分析，并介绍了在体液中对脑特异性糖蛋白进行靶向验证的未来应用。
