Identification of novel brain biomarkers
Identification of novel brain biomarkers
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DOI：
10.1373/clinchem.2006.070912
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发表时间：
2006-09-01
影响因子：
9.3
通讯作者：
Ladenson, Jack H.
中科院分区：
文献类型：
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作者：
Laterza, Omar F.;Modur, Vijay R.;Ladenson, Jack H.
背景：导致脑损伤的疾病（如中风、阿尔茨海默病和帕金森病）的诊断往往存在问题。在这项研究中，我们追求的生物标志物，可能是特定的和敏感的brain injury.Methods的发现：我们进行了基因阵列分析的小鼠模型，寻找生物标志物，都优先和大量产生的大脑。通过生物信息学数据库，我们确定了在大脑中丰富而在其他组织中不丰富的基因的人类同源物。然后，我们确认蛋白质生产的基因，通过蛋白质印迹法的各种组织匀浆和测定的标志物之一，视蛋白样蛋白1（VLP-1），在血浆中的患者缺血性stroke.Results：29个基因，优先和丰富的表达在小鼠大脑中被确定;这29个基因，26人同源。我们集中在17个这些基因和他们的蛋白质产品的基础上，他们的分子特征，新奇，和/或抗体的可用性。Western blot显示这些蛋白质中的13种在脑匀浆中具有强信号。组织特异性进行了测试，通过蛋白质印迹法在人体组织阵列，和一个敏感的和定量的夹心免疫分析，在我们的搜索中观察到的最丰富的基因产物，VLP-1。VLP-1检测中风后患者的血浆中，并在脑脊髓液中的大鼠模型stroke.Conclusions：使用相对mRNA的生产似乎是一种有效的方法，确定可能的生物标志物的组织损伤。Western blot证实了基因表达所提示的组织特异性。其中一种生物标志物VLP-1在大鼠中风模型和中风后患者的血浆中增加。对已确定的候选生物标志物进行更广泛的前瞻性研究似乎是必要的。(c)2006年美国临床化学协会
Background: The diagnosis of diseases leading to brain injury, such as stroke, Alzheimer disease, and Parkinson disease, can often be problematic. In this study, we pursued the discovery of biomarkers that might be specific and sensitive to brain injury.Methods: We performed gene array analyses on a mouse model to look for biomarkers that are both preferentially and abundantly produced in the brain. Via bioinformatics databases, we identified the human homologs of genes that appeared abundant in brain but not in other tissues. We then confirmed protein production of the genes via Western blot of various tissue homogenates and assayed for one of the markers, visinin-like protein 1 (VLP-1), in plasma from patients after ischemic stroke.Results: Twenty-nine genes that were preferentially and abundantly expressed in the mouse brain were identified; of these 29 genes, 26 had human homologs. We focused on 17 of these genes and their protein products on the basis of their molecular characteristics, novelty, and/or availability of antibodies. Western blot showed strong signals in brain homogenates for 13 of these proteins. Tissue specificity was tested by Western blot on a human tissue array, and a sensitive and quantitative sandwich immunoassay was developed for the most abundant gene product observed in our search, VLP-1. VLP-1 was detected in plasma of patients after stroke and in cerebrospinal fluid of a rat model of stroke.Conclusions: The use of relative mRNA production appears to be a valid method of identifying possible biomarkers of tissue injury. The tissue specificity suggested by gene expression was confirmed by Western blot. One of the biomarkers identified, VLP-1, was increased in a rat model of stroke and in plasma of patients after stroke. More extensive, prospective studies of the candidate biomarkers identified appear warranted. (c) 2006 American Association for Clinical Chemistry