CATECHOL THIOETHERS IN PARKINSON'S DISEASE

儿茶酚硫醚在帕金森病中的作用

• 批准号: 6654426
• 负责人: Thomas J Montine
• 金额: $ 27万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6654426
• 关键词: Parkinson's disease; catechols; clinical research; dopamine; environmental toxicology; genetically modified animals; human subject; human tissue; laboratory mouse; neural degeneration; neurotoxins; sulfur aminoacid; thioether; tissue /cell culture

DESCRIPTION: (adapted from applicant's abstract) Parkinson's disease (PD) is a serious public health problem for the United States. Although dramatic advances have been made in the clinical management of Parkinson's disease, understanding of the mechanisms that underlie its neurodegeneration is incomplete. Such knowledge will be necessary for future development of therapeutics that impede or halt the progression of Parkinson's disease. The long-term objectives of this project are to determine the mechanisms by which oxidation products of dopamine and related catechols, catechol thioethers, may be converted to neurotoxins that contribute to nigrostriatal oxidative damage and neurodegeneration. The Specific Aims of this projects are: (1) to determine the potency of endogenous catechol thioether produced in the mercapturic acid pathway and the mechanisms by which they may contribute to dopaminergic neurodegeneration in whole mitochondria, cultured dopaminergic neurons, brain regions of aged control and genetically engineered mice with deficiencies in anti-oxidant defenses, (2) to determine the activities of mercapturic acid pathway enzymes and the concentration of catechol mercapturates in brain regions and CSF from patients with Parkinson's disease, other nigrostriatal neurodegenerative diseases, and aged-matched controls, and (3) to determine the mechanisms by which environmental toxicants epidemiological linked with an increased risk of Parkinson's disease may augment neurotoxicity form catechol thioethers. This new information will determine the extent to which catechol thioethers produced in the mercapturic acid pathway may contribute to Parkinson's disease progression, interact with aging and environmental toxicants implicated in Parkinson's disease, and serve as intra vitam biomarkers of nigrostriatal degeneration.

描述：（改编自申请人的摘要）帕金森病（PD）是一种 美国面临严重的公共卫生问题。虽然戏剧性的进步 在帕金森病的临床管理中， 导致其神经退化的机制并不完整等 知识对于将来开发治疗是必要， 或者阻止帕金森病的发展的长期目标 该项目是确定的机制，通过氧化产物的 多巴胺和相关的儿茶酚，儿茶酚硫醚，可以转化为 导致黑质纹状体氧化损伤的神经毒素， 神经变性本项目的具体目标是：（1）确定 巯基尿酸中产生的内源性儿茶酚硫醚的效力 途径和机制，他们可能有助于多巴胺能 全线粒体神经变性，培养的多巴胺能神经元，脑 老年对照和基因工程小鼠的区域， 抗氧化防御，（2）确定巯基尿酸的活动 途径酶和脑中儿茶酚巯基尿酸盐的浓度 帕金森病患者的区域和CSF，其他黑质纹状体 神经退行性疾病和年龄匹配的对照，以及（3）确定 环境毒物流行病学与一种 帕金森病风险增加可能会增加儿茶酚的神经毒性 硫醚这一新的信息将决定儿茶酚 巯基尿酸途径中产生的硫醚可能有助于 帕金森病进展，与衰老和环境相互作用 帕金森氏病的有毒物质，并作为维生素 黑质纹状体退化的生物标志物。