Biochemistry of PD gene products

PD基因产物的生物化学

• 批准号: 7009781
• 负责人: PETER T LANSBURY
• 金额: $ 38.26万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7009781
• 关键词: Parkinson' s disease; alpha synuclein; chemical genetics; drug design /synthesis /production; drug screening /evaluation; gene mutation; genetic polymorphism; high throughput technology; neurogenetics; protein structure function

This project investigates three PD gene products, alpha-synuclein, UCH-L1 and DJ-1. The approach used is primarily that of in vitro biochemistry. The initial goal in each case is to understand the molecular basis for the effects of PD mutations or polymorphisms. Once a working hypothesis has been generated, we will design high-throughput assays that will allow us to identify drug-like molecules that reverse the effect of the mutation. These assays will be executed in core A. Finally, the working hypothesis will be tested by treating Parkinsonian Drosophila with drug-like molecules (via core B). The long-term (5 year) goal of this project is to confirm the relevance of particular targets for the treatment of PD and, possibly, to develop lead compounds for the development of new PD therapeutics.

该项目研究了三种 PD 基因产物：α-突触核蛋白、UCH-L1 和 DJ-1。使用的方法主要是体外生物化学方法。每种情况的最初目标是了解 PD 突变或多态性影响的分子基础。一旦产生了工作假设，我们将设计高通量测定，使我们能够识别逆转突变效应的药物样分子。这些测定将在核心 A 中执行。最后，将通过用药物样分子（通过核心 B）治疗帕金森果蝇来测试工作假设。该项目的长期（5 年）目标是确认治疗 PD 的特定靶点的相关性，并可能开发用于开发新的 PD 疗法的先导化合物。