Oxidative lipid stress in the brain

大脑中的氧化脂质应激

基本信息

批准号：
8479445
负责人：
Paul H Axelsen
金额：
$ 33.78万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8479445
关键词：
Age Alzheimer&apos s Disease Amyloid Amyloid Fibrils Amyloid beta-Protein Anabolism Animal Model Animals Arachidonic Acids Atherosclerosis Biochemical Brain Brain region Cells Chemicals Complex Diabetes Mellitus Diet Disease Disease Resistance Docosahexaenoic Acids Employee Strikes Future Human In Vitro Intake Intervention Laboratories Lesion Lipids Location Malignant Neoplasms Malnutrition Mass Spectrum Analysis Measures Mediating Membrane Metabolism Morphologic artifacts Mus Nature Neurodegenerative Disorders Oxidative Stress Pathogenesis Pattern Polyunsaturated Fatty Acids Post-Translational Protein Processing Process Production Proteins Radiolabeled Reaction Research Role Running Senile Plaques Series Stress System Testing Thermodynamics Tissues Transgenic Mice amyloid fibril formation amyloidogenesis brain tissue cytotoxic in vivo mouse model neurotoxic oxidation radiotracer response uptake

项目摘要

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.

描述（由申请人提供）：氧化应激似乎与阿尔茨海默氏病的发病机理有关，很可能涉及A之间的相互作用？蛋白质和多不饱和脂肪酰基（PUFA）链。因此，我们建议（1）确定A的表达是否？蛋白质增加了大脑中氧化PUFA代谢和降解的速率，以及脑易于疾病和抗病区域的发生率是否有所不同。（2）测试是否a？蛋白质通常通过脂质氧化产物增加蛋白质的修饰，以及是否a？蛋白质通过脂质氧化产物在体内修饰，这些脂质氧化产物将其聚集成淀粉样蛋白原纤维。（3）测试特定的饮食和药理干预措施是改变容易发生疾病的大脑区域中有毒PUFA降解产物的产生，还是这些地区的PUFA降解产物的命运。我们将利用放射标记的PUFA链，将其注入阿尔茨海默氏病的转基因小鼠模型，以及定量和测序质谱法。