Biochemistry of PD gene products

本项目研究了三种PD基因产物：α-突触核蛋白、UCH-L1和DJ-1。所使用的方法主要是体外生物化学方法。每个病例的初始目标都是了解PD突变或多态效应的分子基础。一旦产生了一个有效的假说，我们将设计高通量的分析方法，使我们能够识别逆转突变影响的类药物分子。这些分析将在核心A中执行。最后，将通过使用类药物分子(通过核心B)治疗帕金森氏症果蝇来检验工作假设。该项目的长期(5年)目标是确认帕金森病治疗的特定目标的相关性，并可能为开发新的帕金森病疗法开发先导化合物。

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.