Facility for drug testing in alpha-syn transgenic drosophila & new models of PD

药物可以改变转基因果蝇的神经退变过程。我们开发了一种方法，可以用来测试数百人，也许在未来，数千人(如果是候选人)，允许采取一种公正的方法。与目前流行的药物发现方法相比，这种方法具有优势，因为可以识别出与帕金森神经变性无关的靶点。我们的第一次筛选，在超过650种FDA批准的药物中，发现了两类抑制帕金森表型的药物。抑制物化合物的大部分(10/12)聚集成这两个 研究小组证实了果蝇作为药物测试模型的实用性。根据目前的文献，这两个班级都不会有活动。这一结果证明了该方法产生关于帕金森病发病机制的新假说的能力。每一类药物的成员都已被证明可以保护哺乳动物神经母细胞瘤细胞免受α-突触核蛋白毒性的影响，支持果蝇与研究哺乳动物疾病的相关性。我们尤德尔中心的核心B部分将支持持续的药物测试，并增加旨在探索饮食脂肪对帕金森病影响的研究。此外，我们计划制作 这一方法适用于其他尤德尔中心的研究人员，用于执行具体的实验，也用于培训他们自己的科学家。这一核心将成为PD研究的独特资源。

Drugs can modify the course of neurodegeneration in ct-synuclein transgenic Drosophila. We developed a method that can be used to test hundreds, and perhaps in the future, thousands (if candidates, allowing an unbiased approach to be taken. This approach has the advantage over the currently prevalent approach to drug discovery in that targets that are not known to be involved in Parkinsonian neurodegeneration can be identified. Our first screen, of over 650 FDA-approved drugs, turned up two classes of drugs that suppress the Parkinsonian phenotype. The fact that most (10/12) of the suppressor compound; clustered into these two groups confirms the utility of Drosophila as a model for drug testing. Neither of these classes was expected to have activity, based on the current literature. This result demonstrates the power of the method for generating new hypotheses concerning PD pathogenesis. Members of each drug class have been demonstrated to protect mammalian neuroblastoma cells against alpha-synuclein toxicity, supporting the relevance of Drosophila for studying mammalian disease. The core B component of our Udall Center will support continued drug testing and the addition of studies aimed at probing the influence of dietary fats on PD. In addition, we plan to make this methodology available to investigators in other Udall centers, both for the execution of specific experiments, and for the training of their own scientists. This core will be a unique resource for PD research.