Department of Chemistry, Center of Membrane Sciences, Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 40506, USA.
Proteomics Clin Appl. 2013 Jan;7(1-2):109-22. doi: 10.1002/prca.201200087.
Proteomics has a wide range of applications, including determination of differences in the proteome in terms of expression and post-translational protein modifications. Redox proteomics allows the identification of specific targets of protein oxidation in a biological sample. Using proteomic techniques, apolipoprotein A-I (ApoA-I) has been found at decreased levels in subjects with a variety of neurodegenerative disorders including in the serum and cerebrospinal fluid (CSF) of Alzheimer disease (AD), Parkinson disease (PD), and Down syndrome (DS) with gout subjects. ApoA-I plays roles in cholesterol transport and regulation of inflammation. Redox proteomics further showed ApoA-I to be highly oxidatively modified and particularly susceptible to modification by 4-hydroxy-2-trans-nonenal (HNE), a lipid peroxidation product. In the current review, we discuss the consequences of oxidation of ApoA-I in terms of neurodegeneration. ROS-associated chemotherapy related ApoA-I oxidation leads to elevation of peripheral levels of tumor necrosis factor-α (TNF-α) that can cross the blood-brain barrier (BBB) causing a signaling cascade that can contribute to neuronal death, likely a contributor to what patients refer to as "chemobrain." Current evidence suggests ApoA-I to be a promising diagnostic marker as well as a potential target for therapeutic strategies in these neurodegenerative disorders.
蛋白质组学有广泛的应用，包括确定蛋白质组在表达和翻译后蛋白质修饰方面的差异。氧化蛋白质组学允许鉴定生物样品中蛋白质氧化的特定靶标。使用蛋白质组学技术，载脂蛋白 A-I（ApoA-I）在包括阿尔茨海默病（AD）、帕金森病（PD）和唐氏综合征（DS）患者的血清和脑脊液（CSF）中的各种神经退行性疾病患者中发现水平降低，痛风患者。ApoA-I 在胆固醇转运和炎症调节中发挥作用。氧化蛋白质组学进一步表明 ApoA-I 高度氧化修饰，特别容易受到 4-羟基-2-反式-壬烯醛（HNE）的修饰，HNE 是一种脂质过氧化产物。在当前的综述中，我们讨论了 ApoA-I 氧化在神经退行性变方面的后果。与 ROS 相关的化疗相关 ApoA-I 氧化导致外周肿瘤坏死因子-α（TNF-α）水平升高，可穿过血脑屏障（BBB），引发信号级联反应，导致神经元死亡，可能是患者所谓的“化疗脑”的原因。目前的证据表明 ApoA-I 是这些神经退行性疾病有希望的诊断标志物以及潜在的治疗靶点。
