LIPID PEROXIDATION, TOXICANTS, AND MITOCHONDRIA

描述（摘自研究者摘要） 脑的神经退行性疾病，如阿尔茨海默病， 帕金森病是美国的主要公共卫生问题。 这些疾病涉及年龄增长，遗传学和 环境因素和生物化学特征，如氧化损伤， 线粒体异常 该项目的长期目标是 通过重点关注以下组成部分来阐明这种关系： 环境毒物、年龄、脂质过氧化和线粒体 功能障碍 本课题的研究假设为：1）反应性烯醛产物 脂质过氧化反应，如HNE，HHE和丙烯醛，有助于 神经退行性疾病的发病机制通过促进线粒体 功能障碍，和2）暴露于环境毒物防止线粒体 烯醛解毒 这些假设将通过成功的 完成以下具体目标：a）确定烯醛的作用 脑线粒体功能，并开发新的保护性烯醇 清除剂; B）确定烯醇类是否增强脑线粒体游离 激进的一代;和，c）建立环境和年龄相关的 影响脑线粒体烯醇解毒途径。 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 年龄相关性神经退行性疾病中的线粒体功能障碍。 与此 知识，新的治疗干预或预防策略， 专为这些疾病而设计。

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.