Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
Acta Neurol Scand. 2010 Nov;122(5):350-9. doi: 10.1111/j.1600-0404.2009.01318.x.
The application of biomarkers may potentially improve the efficiency of the diagnosis for Parkinson's disease (PD). However, no reliable biomarker has been identified to date. This study is aimed to identify proteins that might serve as potential biomarkers for PD diagnosis or pathogenesis.
Two-dimensional difference gel electrophoresis (2D DIGE) technique, in combination with matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), was used to determine the differentially expressed cerebrospinal fluid (CSF) proteins in PD patients (n = 3) compared with normal controls (n = 3). Selected proteins were further confirmed by Western blotting analysis in the CSF of PD patients (n = 8), Alzheimer's disease (AD) patients (n = 6) and normal control subjects (n = 7).
Eight proteins were identified after MS and protein database interrogation. In the CSF of PD patients, the expression levels of one isoform of apolipoprotein A-I (apoA-I), tetranectin, myosin phosphatase target subunit 1 (MYPT1), and two unknown proteins were down-regulated, whereas the expression levels of another apoA-I isoform, proapolipoprotein, and lipoprotein were up-regulated. Western blotting indicates that the expression of tetranectin was reduced in the CSF from PD patients and elevated in AD, while the expression of apoA-I was changed only in the CSF from PD patients.
Our preliminary results suggest that tetranectin and apoA-I may serve as potential biomarkers for PD, though further validation is needed.
生物标志物的应用可能会提高帕金森病 (PD) 的诊断效率。但是，迄今为止尚未发现可靠的生物标志物。本研究旨在鉴定可能作为 PD 诊断或发病机制潜在生物标志物的蛋白质。
采用二维差异凝胶电泳（2D DIGE）技术，结合基质辅助激光解吸/电离飞行时间质谱（MALDI-TOF MS），测定了与正常对照组（n=3）相比 PD 患者（n=3）的脑脊液（CSF）中差异表达的蛋白质。通过 Western blot 分析进一步确认了 CSF 中的选定蛋白质在 PD 患者（n=8）、阿尔茨海默病（AD）患者（n=6）和正常对照组（n=7）中。
经过 MS 和蛋白质数据库检索，鉴定出 8 种蛋白质。在 PD 患者的 CSF 中，载脂蛋白 A-I（apoA-I）的一种同工型、四连接蛋白、肌球蛋白磷酸酶靶亚单位 1（MYPT1）和两种未知蛋白的表达水平下调，而另一种 apoA-I 同工型、前载脂蛋白和脂蛋白的表达水平上调。Western blot 分析表明，四连接蛋白在 PD 患者的 CSF 中表达降低，在 AD 中升高，而 apoA-I 的表达仅在 PD 患者的 CSF 中改变。
我们的初步结果表明，四连接蛋白和 apoA-I 可能作为 PD 的潜在生物标志物，尽管需要进一步验证。
