Parkin is a protein that is disrupted in early onset Parkinson's disease and is believed to function in a cell-protective pathway (called mitophagy), which eliminates faulty mitochondria (powerhouses of the cell) before they can cause damage. However, the role of the parkin pathway in the cells and tissues of our body is unclear because it is extremely difficult to monitor mitophagy in the living body. This study will develop a pre-clinical model to allow us to visualize mitophagy directly.
Mitophagy is disrupted in a specific subset of cells that lack parkin.
We have generated a pre-clinical model to enable us to visualize mitophagy in the brain and we will develop a model without parkin to study mitophagy. The degree of mitophagy will be monitored in distinct neuronal and non-neuronal cells to develop a "mitophagy map" to pinpoint where the parkin pathway is most relevant.
Impact on Diagnosis/Treatment of Parkinson's Disease:
This study will be very important in validating mitophagy as a process that is disrupted in Parkinson's and in determining what kind of brain cells should be targeted by therapy.
Next Steps for Development:
Our system will allow other researchers to validate mitophagy in different models of Parkinson's. Importantly, it will allow the testing of potential pharmaceuticals to prove that they are have the desired effect on mitophagy, a critical step before any therapy can enter clinical trials.