Lifetime proteomic profiling of an A30P alpha-synuclein Drosophila model of Parkinson's disease.
Lifetime proteomic profiling of an A30P alpha-synuclein Drosophila model of Parkinson's disease.
复制标题
帕金森病 A30P α-突触核蛋白果蝇模型的终生蛋白质组学分析。
DOI：
10.1021/pr0700504
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发表时间：
2007
影响因子：
4.4
通讯作者：
Clemmer,DavidE
中科院分区：
文献类型：
--
作者：
Xun,Zhiyin;Sowell,RenaA;Kaufman,ThomasC;Clemmer,DavidE
研究人员对帕金森病（PD）的A30P α-突触核蛋白果蝇模型的蛋白质组变化进行了调查，并将其与年龄匹配的对照组进行了比较。数据是通过鸟枪蛋白质组学方法获得的，该方法包括多维液相色谱、质谱和数据库搜索技术。通过半定量分析来评估果蝇apd模型和年龄匹配对照组之间蛋白表达的相对变化，我们发现28、19、12、5、7、23和17种蛋白在第1、10、20、30、40、50和60天分别有显著差异表达。从所采用的实验方法来看，似乎大多数失调蛋白与年龄的狭窄分布有关，因此与疾病相关的差异在整个生命周期中发生了实质性变化。[J]。蛋白质组学[j] .2007,6, 348]在第1、10和30天显示肌动蛋白细胞骨架蛋白和线粒体蛋白在第1天和第10天的失调，这表明肌动蛋白细胞骨架和线粒体的缺陷与帕金森病的多巴胺能神经元变性有关。对第20、40、50和60天动物的分析支持这样的发现，即这些细胞骨架和线粒体变化在最年轻（症状前和疾病早期）的动物中占主导地位。尽管跨越许多时间点的研究对于表征疾病状态似乎很重要，但了解最年轻年龄的分子变化对于解决病因应该是最重要的。关键词：帕金森病、果蝇、α-突触核蛋白、蛋白质组学、液相色谱、质谱
A survey of the proteome changes in an A30P α-synucleinDrosophilamodel of Parkinson's disease (PD) in comparison to age-matched controls is presented for seven different ages across the adult lifespan. The data were acquired by a shotgun proteomic approach that involves multidimensional liquid chromatographies coupled to mass spectrometry and database searching techniques. Semiquantitative analysis to assess relative changes in protein expression between theDrosophilaPD model and age-matched controls provides evidence that 28, 19, 12, 5, 7, 23, and 17 proteins are significantly differentially expressed at days 1, 10, 20, 30, 40, 50, and 60, respectively. From the experimental approach employed, it appears that most dysregulated proteins are associated with narrow distributions of ages, such that disease-associated differences change substantially across the lifespan. Previous measurements [J. Proteome Res.2007,6, 348] at days 1, 10, and 30 showed dysregulation of actin cytoskeletal proteins at day 1 and mitochondrial proteins at day 10, suggesting that defects in the actin cytoskeleton and the mitochondria are associated with dopaminergic neuron degeneration in PD. Analysis of the day 20, 40, 50, and 60 animals supports the finding that these cytoskeletal and mitochondrial changes predominate in the youngest (pre-symtomatic and early disease stages) animals. Although studies across many time points appear to be important for characterizing disease state, an understanding of molecular changes at the youngest ages should be most important for addressing causation.Keywords: Parkinson's disease •Drosophila• α-synuclein • proteomics • liquid chromatography • mass spectrometry