x -适体技术鉴定血液中的C4A和ApoB是精神分裂症的潜在标志物。

Molecular Neuropsychiatry Pub Date : 2019-03-01 Epub Date: 2018-10-10 DOI:10.1159/000492331
Consuelo Walss-Bass, Ganesh L R Lokesh, Elena Dyukova, David G Gorenstein, David L Roberts, Dawn Velligan, David E Volk
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引用次数: 17

摘要

蛋白质组学作为基因组学方法的一个有希望的替代方法,正在迅速获得领域,以努力解开精神分裂症和其他精神疾病的复杂分子机制。x -适体技术已经成为一种新的蛋白质组学方法,用于高灵敏度分析,我们假设该技术将在精神分裂症患者(n = 60)的血浆样本中识别出与对照组(n = 20)相比独特的分子特征。利用x -适体珠的组合文库,我们开发了一种基于双色流式细胞仪的方法来鉴定对每个目标群体具有高特异性结合的特异性x -适体。在此基础上,我们合成了两个独特的x -适体序列,并通过质谱法鉴定了这些x -适体从患者和对照组中提取的特定蛋白质。我们发现了两种蛋白质生物标志物,补体成分C4A和ApoB,在精神分裂症患者的血浆样本中上调。ELISA验证表明,患者中观察到的C4水平差异可能是由于疾病本身的存在,而载脂蛋白b可能是抗精神病药物引起的改变的标志。这些研究突出了x适体技术在鉴定精神分裂症生物标志物方面的应用,这将促进我们对这种疾病的病理生理机制的理解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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X-Aptamer Technology Identifies C4A and ApoB in Blood as Potential Markers for Schizophrenia.

The field of proteomics is rapidly gaining territory as a promising alternative to genomic approaches in the efforts to unravel the complex molecular mechanisms underlying schizophrenia and other psychiatric disorders. X-aptamer tech-nology has emerged as a novel proteomic approach for high-sensitivity analyses, and we hypothesized that this technology would identify unique molecular signatures in plasma samples from schizophrenia patients (n = 60) compared to controls (n = 20). Using a combinatorial library of X-aptamer beads, we developed a two-color flow cytometer-based approach to identify specific X-aptamers that bound with high specificity to each target group. Based on this, we synthesized two unique X-aptamer sequences, and specific proteins pulled down from the patient and control groups by these X-aptamers were identified by mass spectrometry. We identified two protein biomarkers, complement component C4A and ApoB, upregulated in plasma samples from schizophrenia patients. ELISA validation suggested that the observed differences in C4 levels in patients are likely due to the presence of the illness itself, while ApoB may be a marker of antipsychotic-induced alterations. These studies highlight the utility of the X-aptamer technology in the identification of biomarkers for schizophrenia that will advance our understanding of the pathophysiological mechanisms of this disorder.

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