Biochemistry of PD gene products

本课题研究PD基因的三个产物：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。在每种情况下，最初的目标是了解PD突变或多态性影响的分子基础。一旦产生了一个可行的假设，我们将设计高通量的分析，这将使我们能够识别类似药物的分子，从而逆转突变的影响。这些实验将在核心a中执行。最后，工作假设将通过用药物样分子治疗帕金森果蝇（通过核心B）来验证。该项目的长期（5年）目标是确认PD治疗的特定靶点的相关性，并可能为开发新的PD治疗方法开发先导化合物。

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.