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Quantitative Proteome Analysis of Brain Subregions and Spinal Cord from Experimental Autoimmune Encephalomyelitis Mice by TMT‐Based Mass Spectrometry

机译:基于TMT的质谱法从实验性自身免疫性脑髓炎小鼠中定量蛋白质组织分析和实验性自身免疫性脑髓炎小鼠

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Abstract Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS); its cause is unknown. To understand the pathogenesis of MS, researchers often use the experimental autoimmune encephalomyelitis (EAE) mouse model. Here, the aim is to build a proteome map of the biological changes that occur during MS at the major onset sites—the brain and the spinal cord. Quantitative proteome profiling is performed in five specific brain regions and the spinal cord of EAE and healthy mice with high‐resolution mass spectrometry based on tandem mass tags. On average, 7400 proteins per region are quantified, with the most differentially expressed proteins in the spinal cord (1691), hippocampus (104), frontal cortex (83), cerebellum (63), brainstem (50), and caudate nucleus (41). Moreover, region‐specific and commonly expressed proteins in each region are identified and bioinformatics analysis is performed. Pathway analysis reveals that protein clusters resemble their functions in disease pathogenesis (i.e., by inducing inflammatory responses, immune activation, and cell–cell adhesion). In conclusion, the study provides an understanding of the pathogenesis of MS in the EAE animal model. It is expected that the comprehensive proteome map of the brain and spinal cord can be used to identify biomarkers for the pathogenesis of MS.
机译:摘要多发性硬化症(MS)是中枢神经系统(CNS)的自身免疫性疾病;它的原因是未知的。为了了解MS的发病机制,研究人员经常使用实验性自身免疫性脑脊髓炎(EAE)小鼠模型。这里,目的是建立在主要发病位点的MS期间发生的生物学变化的蛋白质组图 - 脑和脊髓。定量蛋白质组分析在五个特定的脑区和EAE和健康小鼠的脊髓中进行,基于串联质量标签,具有高分辨率质谱。平均而言,定量为7400个蛋白质,在脊髓(1691),海马(104),额叶(83),小脑(63),脑干(50)和尾部(41)中,具有最差异表达的蛋白质。(41 )。此外,鉴定了每个区域中的区域特异性和常规表达蛋白质,进行生物信息学分析。途径分析表明,蛋白质簇类似于疾病发病机制的功能(即,通过诱导炎症反应,免疫活化和细胞粘附)。总之,该研究提供了对EAE动物模型中MS发病机制的理解。预计脑和脊髓的综合蛋白质组地图可用于鉴定MS发病机制的生物标志物。

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