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

α-syn 转基因果蝇药物测试设施

• 批准号: 7312751
• 负责人: PETER T LANSBURY
• 金额: $ 8.83万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7312751
• 关键词: Drosophilidae; Parkinson' s disease; biomedical facility; dietary lipid; disease /disorder model; drug screening /evaluation; genetically modified animals; model design /development

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.

药物可以改变转ct-突触核蛋白果蝇神经退行性变的过程。我们开发了一种方法，可以用来测试数百个，也许在未来，数千个（如果候选人），允许采取公正的方法。这种方法与目前流行的药物发现方法相比具有优势，因为可以识别出与帕金森神经变性有关的未知靶点。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。事实上，大多数（10/12）的抑制化合物；分为这两类