Perluigi Marzia, Joshi Gururaj, Sultana Rukhsana, Calabrese Vittorio, De Marco Carlo, Coccia Raffaella, Cini Chiara, Butterfield D Allan
Department of Biochemical Sciences, University of Rome La Sapienza, Rome, Italy.
J Neurosci Res. 2006 Aug 1;84(2):418-26. doi: 10.1002/jnr.20879.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of amyloid-beta peptide (Abeta), a peptide that as both oligomers and fibrils is believed to play a central role in the development and progress of AD by inducing oxidative stress in brain. Therefore, treatment with antioxidants might, in principle, prevent propagation of tissue damage and neurological dysfunction. The aim of the present study was to investigate the in vivo protective effect of the antioxidant compound ferulic acid ethyl ester (FAEE) against Abeta-induced oxidative damage on isolated synaptosomes. Gerbils were injected intraperitoneally (i.p.) with FAEE or with dimethylsulfoxide, and synaptosomes were isolated from the brain. Synaptosomes isolated from FAEE-injected gerbils and then treated ex vivo with Abeta(1-42) showed a significant decrease in oxidative stress parameters: reactive oxygen species levels, protein oxidation (protein carbonyl and 3-nitrotyrosine levels), and lipid peroxidation (4-hydroxy-2-nonenal levels). Consistent with these results, both FAEE and Abeta(1-42) increased levels of antioxidant defense systems, evidenced by increased levels of heme oxygenase 1 and heat shock protein 72. FAEE led to decreased levels of inducible nitric oxide synthase. These results are discussed with potential therapeutic implications of FAEE, a brain accessible, multifunctional antioxidant compound, for AD involving modulation of free radicals generated by Abeta.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征在于β-淀粉样肽（Aβ）的沉积，这种肽以寡聚体和原纤维形式存在，被认为通过诱导脑内氧化应激在AD的发生和发展中起核心作用。因此，原则上用抗氧化剂治疗可能预防组织损伤和神经功能障碍的进展。本研究的目的是研究抗氧化化合物阿魏酸乙酯（FAEE）对分离的突触体上Aβ诱导的氧化损伤的体内保护作用。给沙鼠腹腔注射（i.p.）FAEE或二甲基亚砜，然后从脑中分离突触体。从注射FAEE的沙鼠中分离出的突触体，然后在体外用Aβ（1-42）处理，结果显示氧化应激参数显著降低：活性氧水平、蛋白质氧化（蛋白质羰基和3-硝基酪氨酸水平）以及脂质过氧化（4-羟基-2-壬烯醛水平）。与这些结果一致，FAEE和Aβ（1-42）均提高了抗氧化防御系统的水平，血红素加氧酶1和热休克蛋白72水平升高证明了这一点。FAEE导致诱导型一氧化氮合酶水平降低。本文讨论了这些结果以及FAEE（一种可进入脑内的多功能抗氧化化合物）对涉及调节由Aβ产生的自由基的AD的潜在治疗意义。
