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: 10005771
• 负责人: Mark Cookson
• 金额: $ 155.9万
• 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/10005771
• 关键词: Brain; Brain region; Cells; Dementia; Deposition; Disease; Disease Marker; Disease Progression; Functional disorder; Genes; Goals; Human; Incidence; Lewy Bodies; Midbrain structure; Mutation; Neurons; Organoids; Parkinson Disease; Pathologic; Play; Process; Proteins; Role; Structure; Toxic effect; Viral Vector; Work; alpha synuclein; in vivo; protein aggregation; receptor; screening; transmission process

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. In ongoing work, we have been probing the mechanism by which a-synuclein is taken up from one cell to another, a process that has been proposed to be important in the spread of disease between brain regions. We have been able to validate one potential receptor that is required for the transmission of proteins in cells and in vivo and are currently working on the underlying mechanisms. We are also working on ways to damage neurons in vivo using a-synuclein, either expressed from viral vectors or by addition of preformed fibrils. As part of this work, we have developed midbrain 'organoids' from human cells. Ongoing work is trying to cross validate results across these platforms.

我们对α-突触核蛋白的研究目前集中在应用大规模筛选方法来了解与这种蛋白质相关的病理生物学，现在已知这种蛋白质不仅是疾病的标志物，而且在疾病进展中发挥积极作用。 在正在进行的工作中，我们一直在探索α-突触核蛋白从一个细胞到另一个细胞的机制，这一过程被认为是大脑区域之间疾病传播的重要过程。我们已经能够验证一种潜在的受体，该受体是细胞和体内蛋白质传输所需的，目前正在研究其潜在机制。 我们还在研究使用α-突触核蛋白在体内损伤神经元的方法，所述α-突触核蛋白由病毒载体表达或通过添加预先形成的原纤维来表达。作为这项工作的一部分，我们已经从人类细胞中开发出了中脑“类器官”。正在进行的工作是试图跨这些平台交叉验证结果。