Quantitative proteomics in A30P*A53T α-synuclein transgenic mice reveals upregulation of Sel1l.

Quantitative proteomics in A30P*A53T α-synuclein transgenic mice reveals upregulation of Sel1l.
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A30PA53T α-突触核蛋白转基因小鼠的定量蛋白质组学揭示了 Sel1l 的上调

DOI:
10.1371/journal.pone.0182092
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发表时间:
2017
期刊:
影响因子:
3.7
通讯作者:
Tian B
Tian B
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Yan J;Zhang P;Jiao F;Wang Q;He F;Zhang Q;Zhang Z;Lv Z;Peng X;Cai H;Tian B

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α-Synuclein is an abundantly expressed neuronal protein that is at the center of focus in understanding a group of neurodegenerative disorders called synucleinopathies, which are characterized by the intracellular presence of aggregated α-synuclein. However, the mechanism of α-synuclein biology in synucleinopathies pathogenesis is not fully understood. In this study, mice overexpressing human A30P*A53T α-synuclein were evaluated by a motor behavior test and count of TH-positive neurons, and then two-dimensional liquid chromatography-tandem mass spectrometry coupled with tandem mass tags (TMTs) labeling was employed to quantitatively identify the differentially expressed proteins of substantia nigra pars compacta (SNpc) tissue samples that were obtained from the α-synuclein transgenic mice and wild type controls. The number of SNpc dopaminergic neurons and the motor behavior were unchanged in A30P*A53T transgenic mice at the age of 6 months. Of the 4,715 proteins identified by proteomic techniques, 271 were differentially expressed, including 249 upregulated and 22 downregulated proteins. These alterations were primarily associated with mitochondrial dysfunction, oxidative stress, ubiquitin-proteasome system impairment, and endoplasmic reticulum (ER) stress. Some obviously changed proteins, which were validated by western blotting and immunofluorescence staining, including Sel1l and Sdhc, may be involved in the α-synuclein pathologies of synucleinopathies. A biological pathway analysis of common related proteins showed that the proteins were linked to a total of 31 KEGG pathways. Our findings suggest that these identified proteins may serve as novel therapeutic targets for synucleinopathies.
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