Alpha Synuclein, cellular dysfunction and Parkinson disease

我们在α-突触核蛋白方面的工作目前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，现在已知它不仅是疾病的标志，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转移到另一个细胞的机制，这一过程被认为在疾病在大脑区域之间的传播中起着重要作用。我们已经能够验证一种潜在的受体，它是蛋白质在细胞和体内传递所必需的，目前正在研究其潜在的机制。 我们还在研究使用α-突触核蛋白损伤体内神经元的方法，这种蛋白可以是通过病毒载体表达的，也可以是通过添加预先形成的纤维来实现的。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在这些平台上交叉验证结果。

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.