The exact cause of brain cell death in people with Parkinson's disease (PD) is not fully understood. Studies have revealed clumps of protein alpha-synuclein in brain cells. Modified alpha-synuclein -- a protein present in healthy brain cells in small amounts -- builds up and clumps in the cells of people with PD. The function of modified alpha-synuclein and the reason for its buildup in Parkinson's remain unknown.
Identifying proteins that interact with modified alpha-synuclein in healthy cells will allow us to understand how modified alpha-synuclein works and why it builds up in cells of people with PD.
We aim to collect modified alpha-synuclein from healthy brains using a novel technique and identify proteins that interact with it. The level of these protein interactions in brain cells can then be changed, which could show us why modified alpha-synuclein clumps. Once we understand this process in healthy cells, we will work with disease models to alter alpha-synuclein or proteins it interacts with to observe if we can repair damaged cells to prevent their death.
Impact on Diagnosis/Treatment of Parkinson's Disease:
These findings will help us develop new drugs to prevent modified alpha-synuclein accumulation in brain cells and, therefore, the progression of cell death associated with Parkinson's disease.
Next Steps for Development:
Our next steps would be to confirm our results in more sophisticated pre-clinical models of PD. This will allow us to understand if our hypothesis holds true regardless of the model we use.