LIPID PEROXIDATION, TOXICANTS, AND MITOCHONDRIA

脂质过氧化、毒物和线粒体

• 批准号: 6652467
• 负责人: MATTHEW J PICKLO
• 金额: $ 10.8万
• 依托单位: UNIVERSITY OF NORTH DAKOTA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-15 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6652467
• 关键词: Alzheimer's disease; Parkinson's disease; acrolein; aging; alkenes; brain cell; cell line; detoxification; environmental toxicology; free radical scavengers; gene targeting; genetically modified animals; hazardous substances; laboratory rat; lipids; mitochondria; mitochondrial disease /disorder; neural degeneration; neurophysiology; neurotoxicology; neurotoxins; pathologic process; peroxidation

DESCRIPTION (Taken from the Investigator's Abstract) Neurodegenerative diseases of the brain such as Alzheimer's disease and Parkinson's disease are major public health problems in the United States. These diseases involve a complex orchestration of advancing age, genetics, and environmental factors and biochemical features such as oxidative damage and mitochondrial abnormalities. The long term objective of this project is to elucidate this relationship by focusing on the following components: environmental toxicants, age, lipid peroxidation, and mitochondrial dysfunction. The hypotheses of this project are 1) reactive alkenal products of lipid peroxidation, such as HNE, HHE, and acrolein, contribute to the pathogenesis of neurodegenerative disease by promoting mitochondrial dysfunction, and 2) exposure to environmental toxicants prevent mitochondrial alkenal detoxification. These hypotheses will be tested through successful completion of the following specific aims: a) define the effects of alkenals on brain mitochondrial functions and develop novel protective alkenal scavengers; b) determine whether alkenals enhance brain mitochondrial free radical generation; and, c) establish the environmental and age-related influences on brain mitochondrial alkenal detoxifying pathways. Successful completion of these experiments will provide fundamental information concerning the relationship of environmental factors, oxidative damage, and mitochondrial dysfunction in age-related neurodegenerative disease. With this knowledge, novel therapeutic interventions or preventative strategies may be designed for these diseases.

描述（取自研究者的摘要） 大脑的神经退行性疾病，例如阿尔茨海默氏病和 帕金森氏病是美国的主要公共卫生问题。 这些疾病涉及促进年龄，遗传学和 环境因素和生化特征，例如氧化损伤和 线粒体异常。 该项目的长期目标是 通过关注以下组成部分来阐明这种关系： 环境有毒物质，年龄，脂质过氧化和线粒体 功能障碍。 该项目的假设是1）反应性烷烃产品 脂质过氧化（例如HNE，HHE和丙烯醛）的 通过促进线粒体的神经退行性疾病的发病机理 功能障碍和2）暴露于环境有毒物质预防线粒体 烷烃排毒。 这些假设将通过成功检验 完成以下特定目的的完成：a）定义烷烃的影响 在脑线粒体功能上，发展新型保护性烷烃 清道夫； b）确定烷烃是否增强了脑线粒体不含 激进的一代；以及，c）建立环境和年龄有关 对脑线粒体烷烃排毒途径的影响。 成功的 这些实验的完成将提供基本信息 关于环境因素的关系，氧化损伤和 与年龄有关的神经退行性疾病的线粒体功能障碍。 与此 知识，新颖的治疗干预措施或预防策略可能是 专为这些疾病而设计。