a Department of Chemistry , University of Aveiro , Aveiro , Portugal.
b Department of Medical Sciences , Institute for Biomedicine - iBiMED, University of Aveiro , Aveiro , Portugal.
Crit Rev Clin Lab Sci. 2017 May;54(3):185-204. doi: 10.1080/10408363.2017.1299682. Epub 2017 Apr 10.
Cerebrospinal fluid (CSF) is an excellent source of biological information regarding the nervous system, once it is in close contact and accurately reflects alterations in this system. Several studies have analyzed differential protein profiles of CSF samples between healthy and diseased human subjects. However, the pathophysiological mechanisms and how CSF proteins relate to diseases are still poorly known. By applying bioinformatics tools, we attempted to provide new insights on the biological and functional meaning of proteomics data envisioning the identification of putative disease biomarkers. Bioinformatics analysis of data retrieved from 99 mass spectrometry (MS)-based studies on CSF profiling highlighted 1985 differentially expressed proteins across 49 diseases. A large percentage of the modulated proteins originate from exosome vesicles, and the majority are involved in either neuronal cell growth, development, maturation, migration, or neurotransmitter-mediated cellular communication. Nevertheless, some diseases present a unique CSF proteome profile, which were critically analyzed in the present study. For instance, 48 proteins were found exclusively upregulated in the CSF of patients with Alzheimer's disease and are mainly involved in steroid esterification and protein activation cascade processes. A higher number of exclusively upregulated proteins were found in the CSF of patients with multiple sclerosis (76 proteins) and with bacterial meningitis (70 proteins). Whereas in multiple sclerosis, these proteins are mostly involved in the regulation of RNA metabolism and apoptosis, in bacterial meningitis the exclusively upregulated proteins participate in inflammation and antibacterial humoral response, reflecting disease pathogenesis. The exploration of the contribution of exclusively upregulated proteins to disease pathogenesis will certainly help to envision potential biomarkers in the CSF for the clinical management of nervous system diseases.
脑脊液（CSF）是神经系统的重要生物信息来源，因为它与神经系统密切接触，并能准确反映神经系统的变化。有几项研究分析了健康和患病人类受试者的 CSF 样本中差异蛋白图谱。然而，CSF 蛋白与疾病的病理生理机制及其相关性仍知之甚少。通过应用生物信息学工具，我们试图提供对蛋白质组学数据的生物学和功能意义的新见解，以期确定潜在的疾病生物标志物。对从 99 项基于 MS 的 CSF 分析研究中检索到的数据进行的生物信息学分析，突出了 49 种疾病中 1985 种差异表达蛋白。大量调节蛋白来源于外泌体囊泡，其中大多数与神经元细胞的生长、发育、成熟、迁移或神经递质介导的细胞通讯有关。然而，一些疾病具有独特的 CSF 蛋白质组谱，本研究对此进行了批判性分析。例如，在阿尔茨海默病患者的 CSF 中发现了 48 种蛋白特异性上调，这些蛋白主要参与类固醇酯化和蛋白激活级联过程。多发性硬化症（76 种蛋白）和细菌性脑膜炎（70 种蛋白）患者的 CSF 中发现了更多的特异性上调蛋白。在多发性硬化症中，这些蛋白主要参与 RNA 代谢和细胞凋亡的调节，而在细菌性脑膜炎中，特异性上调蛋白参与炎症和抗菌体液反应，反映了疾病的发病机制。探索特异性上调蛋白对疾病发病机制的贡献，必将有助于设想 CSF 中潜在的神经疾病临床管理的生物标志物。
