Alpha Synuclein, cellular dysfunction and Parkinson disease

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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.