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: 8931626
• 负责人: Mark Cookson
• 金额: $ 58.45万
• 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/8931626
• 关键词: Biological Assay; Brain; Cells; Dementia; Deposition; Disease; Disease Marker; Disease Progression; Functional disorder; Gene-Modified; Genes; Goals; Image; Incidence; Label; Lewy Bodies; Libraries; Mutation; Neurons; Parkinson Disease; Play; Proteins; Role; Small Interfering RNA; Structure; Toxic effect; Work; alpha synuclein; cell type; fluorophore; protein aggregation; screening; synuclein; uptake

Our work on a-synuclein is currently focussed on applying large scale screening approaches to understand the pathobiology associated with this protein, which is now known to not only be a marker of disease but also plays an active role in disease progression. We have been working on high content imaging approaches to follow synuclein uptake and toxicity in cells in culture. We have been able to show that a variety of cell types can uptake preformed fibrils that are labelled with fluorophores to allow for simple assays of internalization. The ongoing objective of the work is to port this assay into a multi well format so we can then screen siRNA libraries for genes that modify uptake.

我们对a-synuclein的研究目前主要集中在应用大规模筛选方法来了解与该蛋白相关的病理生物学，目前已知该蛋白不仅是疾病的标志物，而且在疾病进展中起着积极作用。我们一直在研究高含量成像方法，以跟踪突触核蛋白在培养细胞中的摄取和毒性。我们已经能够证明，各种类型的细胞可以摄取预先形成的原纤维，这些原纤维被荧光团标记，以便进行简单的内化分析。这项工作正在进行的目标是将该分析移植到多孔格式，这样我们就可以筛选修饰摄取基因的siRNA文库。