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首页> 外文期刊>Molecular brain >Anatomo-proteomic characterization of human basal ganglia: focus on striatum and globus pallidus
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Anatomo-proteomic characterization of human basal ganglia: focus on striatum and globus pallidus

机译：人基底神经节的解剖蛋白质组学表征：专注于纹状体和苍白球

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Background The basal ganglia (BG) are a complex network of subcortical nuclei involved in the coordination and integration of the motor activity. Although these independent anatomical structures are functionally related, the proteome present in each isolated nucleus remains largely unexplored. In order to analyse the BG proteome in a large-scale format, we used a multi-dimensional fractionation approach which combines isolation of anatomically-defined nuclei, and protein/peptide chromatographic fractionation strategies coupled to mass spectrometry. Results Using this workflow, we have obtained a proteomic expression profile across striatum and globus pallidus structures among which 1681 proteins were located in caudate nucleus (CN), 1329 in putamen, 1419 in medial globus pallidus (GPi), and 1480 in lateral globus pallidus (GPe), establishing a BG reference proteome to a depth of 2979 unique proteins. Protein interactome mapping highlighted significant clustering of common proteins in striatal and pallidal structures, contributing to oxidative phosphorylation, protein degradation and neurotrophin signalling pathways. In silico analyses emphasized specific pathways represented in striatal and pallidal structures highlighting 5-hydroxytryptamine degradation, synaptic vesicle trafficking, and dopamine, metabotropic glutamate and muscarinic acetylcholine receptor pathways. Additional bioinformatic analyses also revealed that: i) nearly 4% of identified proteins have been previously associated to neurodegenerative syndromes, ii) 11% of protein set tends to localize to synaptic terminal, and iii) 20% of identified proteins were also localized in cerebrospinal fluid (CSF). Conclusions Overall, the anatomo-proteomic profiling of BG complements the anatomical atlas of the human brain transcriptome, increasing our knowledge about the molecular basis of the BG and the etiology of the movement disorders.
机译：背景基底神经节（BG）是皮层下核的复杂网络，参与运动活动的协调和整合。尽管这些独立的解剖结构在功能上相关，但每个分离的核中存在的蛋白质组仍未开发。为了以大规模形式分析BG蛋白质组，我们使用了多维分馏方法，该方法将解剖学定义的核的分离与蛋白质/肽色谱分馏策略结合质谱相结合。结果使用此工作流程，我们获得了横跨纹状体和苍白球结构的蛋白质组学表达谱，其中在尾状核（CN）中存在1681个蛋白质，在壳状核中位于1329，在苍白球内侧（GPi）中存在1419，在苍白球外侧中存在1480。 （GPe），建立BG参考蛋白质组到2979种独特蛋白质的深度。蛋白质相互作用组作图突出了纹状体和苍白质结构中常见蛋白质的显着聚集，这有助于氧化磷酸化，蛋白质降解和神经营养蛋白信号通路。在计算机分析中强调了以纹状体和苍白质结构为代表的特定途径，突出了5-羟色胺降解，突触小泡运输和多巴胺，代谢型谷氨酸和毒蕈碱型乙酰胆碱受体途径。其他生物信息学分析还显示：i）之前已鉴定出的蛋白质中有近4％与神经退行性综合症有关; ii）蛋白质组中有11％的蛋白质倾向于定位于突触末端，iii）所鉴定的蛋白质中的20％也位于脑脊髓中液体（CSF）。结论总体而言，BG的解剖蛋白质组图谱可补充人脑转录组的解剖图谱，从而增加了我们对BG分子基础和运动障碍病因的认识。

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