Sizova Daria, Charbaut Elodie, Delalande François, Poirier Florence, High Anthony A, Parker Fabienne, Van Dorsselaer Alain, Duchesne Marc, Diu-Hercend Anita
Alzheimer's Disease Group, Paris Research Centre, Aventis Pharma, 94403 Vitry sur Seine Cedex, France.
Neurobiol Aging. 2007 Mar;28(3):357-70. doi: 10.1016/j.neurobiolaging.2006.01.011. Epub 2006 Mar 7.
We used a beta-amyloid precursor protein (APP) transgenic (Tg) mouse model that displays some of the typical Alzheimer-associated pathological features to study the brain proteoma associated with amyloid plaque deposition. Two groups (male and female) of 14-month-old Tg mice were compared with their wild type littermates. We used differential 2D electrophoresis coupled with mass spectrometry to generate one of the first complete image of changes in brain protein expression occurring in this well-recognized model of Alzheimer's disease (AD). We identified 15 different proteins, which are significantly regulated in this pathology (p<0.05, > or =1.5-fold variation in expression comparing with the wild type samples). These comprise a number of proteins that were already known to be implicated in AD and neurodegeneration, as well as several proteins which relationship with AD had not been shown before. Identified proteins were grouped according to their biological key pathways. Results obtained are discussed in view of existing bibliographic data on human AD transcriptoma and proteoma.
我们使用了一种β-淀粉样前体蛋白(APP)转基因(Tg)小鼠模型,该模型呈现出一些典型的与阿尔茨海默病相关的病理特征,以研究与淀粉样斑块沉积相关的脑蛋白质组。将两组(雄性和雌性)14个月大的Tg小鼠与其野生型同窝小鼠进行比较。我们使用差异二维电泳结合质谱分析法,生成了在这个公认的阿尔茨海默病(AD)模型中发生的脑蛋白表达变化的首批完整图谱之一。我们鉴定出15种不同的蛋白质,它们在这种病理状态下受到显著调节(p<0.05,与野生型样本相比,表达变化≥1.5倍)。这些蛋白质包括一些已知与AD和神经退行性变有关的蛋白质,以及几种之前未显示与AD有联系的蛋白质。根据其生物学关键途径对鉴定出的蛋白质进行分组。鉴于现有的关于人类AD转录组和蛋白质组的文献数据,对所得结果进行了讨论。