Department of Chemistry, University of Kentucky , Lexington, KY, USA.
Antioxid Redox Signal. 2010 Mar;12(3):327-36. doi: 10.1089/ars.2009.2810.
Previous studies indicated increased levels of protein oxidation in brain from subjects with Alzheimer's disease (AD), raising the question of whether oxidative damage is a late effect of neurodegeneration or precedes and contributes to the pathogenesis of AD. Hence, in the present study we used a parallel proteomic approach to identify oxidatively modified proteins in inferior parietal lobule (IPL) from subjects with mild cognitive impairment (MCI) and early stage-AD (EAD). By comparing to age-matched controls, we reasoned that such analysis could help in understanding potential mechanisms involved in upstream processes in AD pathogenesis. We have identified four proteins that showed elevated levels of protein carbonyls: carbonic anhydrase II (CA II), heat shock protein 70 (Hsp70), mitogen-activated protein kinase I (MAPKI), and syntaxin binding protein I (SBP1) in MCI IPL. In EAD IPL we identified three proteins: phosphoglycerate mutase 1 (PM1), glial fibrillary acidic protein, and fructose bisphospate aldolase C (FBA-C). Our results imply that some of the common targets of protein carbonylation correlated with AD neuropathology and suggest a possible involvement of protein modifications in the AD progression.
先前的研究表明，阿尔茨海默病（AD）患者大脑中的蛋白质氧化水平升高，这引发了一个问题，即氧化损伤是神经退行性变的晚期效应，还是先于并促成 AD 的发病机制。因此，在本研究中，我们使用平行蛋白质组学方法来鉴定轻度认知障碍（MCI）和早期 AD（EAD）患者顶下小叶（IPL）中的氧化修饰蛋白。通过与年龄匹配的对照组进行比较，我们推断这种分析可以帮助理解 AD 发病机制上游过程中涉及的潜在机制。我们已经鉴定出四种蛋白的羰基水平升高：碳酸酐酶 II（CA II）、热休克蛋白 70（Hsp70）、丝裂原激活蛋白激酶 I（MAPKI）和突触结合蛋白 I（SBP1）在 MCI IPL 中。在 EAD IPL 中，我们鉴定出三种蛋白：磷酸甘油酸变位酶 1（PM1）、神经胶质纤维酸性蛋白和果糖双磷酸醛缩酶 C（FBA-C）。我们的结果表明，与 AD 神经病理学相关的蛋白质羰基的一些常见靶标，并表明蛋白质修饰可能参与 AD 的进展。
