Proteome response to the panneural expression of human wild-type alpha-synuclein: a Drosophila model of Parkinson's disease.
Proteome response to the panneural expression of human wild-type alpha-synuclein: a Drosophila model of Parkinson's disease.
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DOI：
10.1021/pr800207h
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发表时间：
2008-09
影响因子：
4.4
通讯作者：
Clemmer, David E.
中科院分区：
文献类型：
--
作者：
Xun, Zhiyin;Kaufman, Thomas C.;Clemmer, David E.
α-突触核蛋白与包括帕金森病（PD）在内的几种神经退行性疾病有关。在人类中，只有突变形式的α-突触核蛋白与PD相关;然而，人类野生型（WT）α-突触核蛋白的泛神经表达在果蝇中诱导帕金森样症状。在这里，我们报告了一个定量蛋白质组学分析的WT α-突触核蛋白转基因果蝇与年龄匹配的控制在症状前阶段，利用全球同位素标记策略结合多维液相色谱和串联质谱。该分析包括两个生物学重复，其中样品在正向和反向方向上进行同位素标记。总共有229种蛋白质从至少两种肽序列的分配中定量。其中，188（82%）蛋白质检测正向和反向标记测量。发现12种蛋白质响应于人WT α-突触核蛋白的表达而差异表达;通过Western印迹分析证实了幼虫血清蛋白2和脂肪体蛋白1水平的下调。基因本体论分析表明，失调的蛋白质主要与细胞代谢和信号传导相关，表明代谢和信号传导途径的扰动对PD的潜在贡献。在症状前WT α-突触核蛋白表达动物中也观察到通常在PD患者脑中发现的铁（III）结合蛋白铁蛋白水平升高。在病理相关蛋白和新蛋白中观察到的改变可能揭示α-突触核蛋白的病理作用，这可能导致在症状前阶段诊断策略的发展。
The α-synuclein protein is associated with several neurodegenarative diseases, including Parkinson’s disease (PD). In humans, only mutated forms of α-synuclein are linked to PD; however, panneural expression of human wild-type (WT) α-synuclein induces Parkinson’s like-symptoms in Drosophila. Here, we report a quantitative proteomic analysis of WT α-synuclein transgenic flies with age-matched controls at the presymptomatic stage utilizing a global isotopic labeling strategy combined with multidimensional liquid chromatographies and tandem mass spectrometry. The analysis includes two biological replicates, in which samples are isotopically labeled in forward and reverse directions. In total, 229 proteins were quantified from assignments of at least two peptide sequences. Of these, 188 (82%) proteins were detected in both forward and reverse labeling measurements. Twelve proteins were found to be differentially expressed in response to the expression of human WT α-synuclein; down-regulations of larval serum protein 2 and fat body protein 1 levels were confirmed by Western blot analysis. Gene Ontology analysis indicates that the dysregulated proteins are primarily associated with cellular metabolism and signaling, suggesting potential contributions of perturbed metabolic and signaling pathways to PD. An increased level of the iron (III)-binding protein, ferritin, typically found in the brains of PD patients, is also observed in presymptomatic WT α-synuclein expressing animals. The observed alterations in both pathology-associated and novel proteins may shed light on the pathological roles of α-synuclein that may lead to the development of diagnostic strategies at the presymptomatic stage.
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影响因子：
16.2
作者：
Giasson, BI;Duda, JE;Lee, VMY
通讯作者：
Lee, VMY
影响因子：
3.3
作者：
Harsing, LG;Zigmond, MJ
通讯作者：
Zigmond, MJ
影响因子：
64.5
作者：
ARBER, S;HALDER, G;CARONI, P
通讯作者：
CARONI, P
影响因子：
168.9
作者：
Ibáñez, P;Bonnet, AM;Brice, A
通讯作者：
Brice, A
DOI：
10.1002/dvg.1020070103
发表时间：
1986-01-01
期刊：
DEVELOPMENTAL GENETICS
影响因子：
--
作者：
KUHN, DT;CUNNINGHAM, GN
通讯作者：
CUNNINGHAM, GN