Korolainen Minna A, Auriola Seppo, Nyman Tuula A, Alafuzoff Irina, Pirttilä Tuula
Department of Neuroscience and Neurology, University of Kuopio, Harjulantie 1D, P.O. Box 1627, FIN-70211 Kuopio, Finland.
Neurobiol Dis. 2005 Dec;20(3):858-70. doi: 10.1016/j.nbd.2005.05.021. Epub 2005 Jun 27.
Chronic inflammation is known to play an important role in the heterogeneous pathogenesis of Alzheimer's disease (AD). Activated astrocytes expressing glial fibrillary acidic protein (GFAP) are closely associated with AD pathology, such as tangles, neuritic plaques and amyloid depositions. Altogether, 46 soluble isoforms of GFAP were separated and most of them quantified by two-dimensional immunoblotting in frontal cortices of AD patients and age-matched controls. A 60% increase in the amount of more acidic isoforms of GFAP was observed in AD and these isoforms were both phosphorylated and N-glycosylated, while more basic isoforms were O-glycosylated and exhibited no quantitative differences between post-mortem AD and control brains. These data highlight the importance of exploring isoform-specific levels of proteins in pathophysiological conditions since modifications of proteins determine their activity state, localization, turnover and interaction with other molecules. Mechanisms, structures and functional consequences of modification of GFAP isoforms remain to be clarified.
已知慢性炎症在阿尔茨海默病（AD）的异质性发病机制中起重要作用。表达胶质纤维酸性蛋白（GFAP）的活化星形胶质细胞与AD病理学密切相关，如缠结、神经炎性斑块和淀粉样蛋白沉积。共分离出46种GFAP可溶性异构体，其中大部分通过二维免疫印迹法在AD患者和年龄匹配的对照者的额叶皮质中进行定量。在AD患者中观察到GFAP酸性更强的异构体数量增加了60%，这些异构体同时发生了磷酸化和N-糖基化，而碱性更强的异构体发生了O-糖基化，且在AD患者死后大脑和对照大脑之间没有表现出定量差异。这些数据突出了在病理生理条件下探索蛋白质异构体特异性水平的重要性，因为蛋白质修饰决定了它们的活性状态、定位、周转以及与其他分子的相互作用。GFAP异构体修饰的机制、结构和功能后果仍有待阐明。
