Oxidative lipid stress in the brain

描述（由申请人提供）：氧化应激似乎参与阿尔茨海默病的发病机制，最有可能涉及A？蛋白质和多不饱和脂肪酰基（PUFA）链。因此，我们建议（1）确定是否表达的A？蛋白质增加脑中PUFA的氧化代谢和降解速率，以及在脑的疾病易感区和疾病抵抗区的速率是否不同;蛋白质增加蛋白质修饰的脂质氧化产物一般，是否A？蛋白质在体内被脂质氧化产物修饰，脂质氧化产物加速蛋白质聚集成淀粉样纤维;和（3）测试特定的饮食和药物干预是否改变易患病脑区域中有毒PUFA降解产物的产生，或改变PUFA降解产物在这些区域中的命运。我们将利用放射性标记的PUFA链，将其注射到阿尔茨海默病的转基因小鼠模型中，以及定量和测序质谱。

DESCRIPTION (provided by applicant): Oxidative stress appears to be involved in the pathogenesis of Alzheimer's disease, and most likely involves interactions between A? proteins and polyunsaturated fatty acyl (PUFA) chains. Therefore, we are proposing to (1) determine whether the expression of A? proteins increases the rate of oxidative PUFA metabolism and degradation in brain, and whether the rates differ in disease-prone and disease-resistant regions of brain; (2) test whether A? proteins increase protein modification by lipid oxidation products in general, and whether A? proteins are modified in vivo by the lipid oxidation products that accelerate their aggregation into amyloid fibrils; and (3) test whether specific dietary and pharmacological interventions alter the production of toxic PUFA degradation products in disease-prone brain regions, or the fate of PUFA degradation products in these regions. We will make use of radiolabeled PUFA chains, which will be injected into transgenic mouse models of Alzheimer's disease, as well as quantitative and sequencing mass spectrometry.