Alpha Synuclein, cellular dysfunction and Parkinson disease

α 突触核蛋白、细胞功能障碍和帕金森病

• 批准号: 8736655
• 负责人: Mark Cookson
• 金额: $ 42.24万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 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/8736655
• 关键词: Acute; Address; Biological Models; Brain; Cell Line; Cells; Dementia; Deposition; Disease; Functional disorder; Genes; Goals; Incidence; Laboratories; Length; Lewy Bodies; Measures; Modeling; Mutation; Neurons; Paper; Parkinson Disease; Proteins; Publications; Reporting; Structure; System; Testing; Time; Toxic effect; alpha synuclein; protein aggregation; tau Proteins

Several laboratories using different model systems have approached understanding why alpha-synuclein is toxic to cells. Our approach has been to develop a mammalian system where we can induce alpha-synuclein protein over several days with the long term goal of then finding genes that can block the effect. In parallel, we made cell lines expressing tau. Despite several previous publications supporting an acute toxic effect, we have fairly modest toxicity in our model. We are therefore addressing different strategies to recover modifiers. These include testing genes that are reported to worsen alpha-synuclein toxicity from previous papers, trying different measures of toxicity, and increasing the length of time for which toxic proteins are expressed.

使用不同模型系统的几个实验室已经接近理解为什么α-突触核蛋白对细胞有毒。我们的方法是开发一种哺乳动物系统，在那里我们可以在几天内诱导α-突触核蛋白，长期目标是找到可以阻断这种效应的基因。同时，我们制备了表达tau的细胞系。尽管之前的几篇出版物支持急性毒性作用，但我们在模型中的毒性相当温和。因此，我们正在解决不同的策略来恢复修改器。这些措施包括测试先前论文中报道的恶化α-突触核蛋白毒性的基因，尝试不同的毒性措施，以及增加有毒蛋白表达的时间长度。