Quantitative proteomic analysis of Niemann-Pick disease, type C1 cerebellum identifies protein biomarkers and provides pathological insight.
Quantitative proteomic analysis of Niemann-Pick disease, type C1 cerebellum identifies protein biomarkers and provides pathological insight.
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DOI：
10.1371/journal.pone.0047845
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Porter FD
中科院分区：
文献类型：
--
作者：
Cologna SM;Jiang XS;Backlund PS;Cluzeau CV;Dail MK;Yanjanin NM;Siebel S;Toth CL;Jun HS;Wassif CA;Yergey AL;Porter FD
C1型尼曼-皮克病（NPC 1）是一种致命的神经退行性疾病，目前尚无明确的治疗方法。在NPC 1中，包括神经炎症、氧化应激和神经元凋亡的病理级联反应可能有助于临床表型。虽然NPC 1的遗传原因是已知的，我们试图通过鉴定NPC 1突变小鼠小脑中差异表达的蛋白质来进一步了解其病理生理学。采用双向凝胶电泳和质谱分析，77差异表达的蛋白质在Npc 1突变小鼠小脑相比，对照组。这些包括参与葡萄糖代谢、解毒/氧化应激和阿尔茨海默病相关蛋白的蛋白质。此外，脂肪酸结合蛋白家族的成员，包括FABP 3，FABP 5和FABP 7，被发现在Npc 1突变体小脑相对于对照的表达发生了改变。将我们的研究结果从小鼠模型翻译到患者，我们证实了NPC 1患者脑脊液中谷胱甘肽S-转移酶α、超氧化物歧化酶和FABP 3的表达相对于儿科对照发生了变化。与未接受麦格司他治疗的患者相比，接受麦格司他（一种鞘糖脂合成抑制剂）治疗的NPC 1患者亚组显示FABP 3水平显著降低。这项研究提供了NPC 1中失调蛋白的初步报告，这将有助于进一步研究NPC 1的病理学，并促进治疗试验的实施。
Niemann-Pick disease, type C1 (NPC1) is a fatal, neurodegenerative disorder for which there is no definitive therapy. In NPC1, a pathological cascade including neuroinflammation, oxidative stress and neuronal apoptosis likely contribute to the clinical phenotype. While the genetic cause of NPC1 is known, we sought to gain a further understanding into the pathophysiology by identifying differentially expressed proteins in Npc1 mutant mouse cerebella. Using two-dimensional gel electrophoresis and mass spectrometry, 77 differentially expressed proteins were identified in Npc1 mutant mice cerebella compared to controls. These include proteins involved in glucose metabolism, detoxification/oxidative stress and Alzheimer disease-related proteins. Furthermore, members of the fatty acid binding protein family, including FABP3, FABP5 and FABP7, were found to have altered expression in the Npc1 mutant cerebellum relative to control. Translating our findings from the murine model to patients, we confirm altered expression of glutathione s-transferase α, superoxide dismutase, and FABP3 in cerebrospinal fluid of NPC1 patients relative to pediatric controls. A subset of NPC1 patients on miglustat, a glycosphingolipid synthesis inhibitor, showed significantly decreased levels of FABP3 compared to patients not on miglustat therapy. This study provides an initial report of dysregulated proteins in NPC1 which will assist with further investigation of NPC1 pathology and facilitate implementation of therapeutic trials.
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DOI：
10.1126/science.1161070
发表时间：
2008-09-05
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Lata S;Schoehn G;Jain A;Pires R;Piehler J;Gottlinger HG;Weissenhorn W
通讯作者：
Weissenhorn W
DOI：
10.1523/jneurosci.1317-11.2011
发表时间：
2011-06-22
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Aqul A;Liu B;Ramirez CM;Pieper AA;Estill SJ;Burns DK;Liu B;Repa JJ;Turley SD;Dietschy JM
通讯作者：
Dietschy JM
影响因子：
3
作者：
Duncan D;Prodduturi N;Zhang B
通讯作者：
Zhang B
影响因子：
3.7
作者：
Davidson CD;Ali NF;Micsenyi MC;Stephney G;Renault S;Dobrenis K;Ory DS;Vanier MT;Walkley SU
通讯作者：
Walkley SU
影响因子：
2.9
作者：
Boneva, Nadezhda B.;Mori, Yoshimi;Yamashima, Tetsumori
通讯作者：
Yamashima, Tetsumori