LIPID PEROXIDATION, TOXICANTS, AND MITOCHONDRIA

描述(摘自调查人员摘要) 大脑的神经退行性疾病，如阿尔茨海默病和 帕金森氏症是美国的主要公共卫生问题。 这些疾病涉及到年龄增长、遗传和 环境因素和生化特征，如氧化损伤和 线粒体异常。这个项目的长期目标是 通过关注以下几个组成部分来阐明这种关系： 环境毒物、AGE、脂质过氧化和线粒体 功能障碍。这个项目的假设是1)反应性的烯烃产品 脂质过氧化，如HNE、HHE和丙烯醛，有助于 促进线粒体功能的神经退行性疾病的发病机制 功能障碍，以及2)暴露在环境毒物中会阻止线粒体 烯烃解毒。这些假设将通过成功的 完成下列具体目标：a)确定烯烃的影响 脑线粒体功能与开发新型保护性烯烃 清道夫；b)确定烯烃是否促进脑线粒体自由 激进的一代；以及，c)建立与环境和年龄有关的 对脑线粒体烯烃解毒途径的影响。成功 这些实验的完成将提供基本信息 关于环境因素、氧化损伤和 老年性神经退行性疾病中的线粒体功能障碍。有了这个 知识、新的治疗干预措施或预防策略可能是 专为这些疾病设计的。

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.