Neurons of the substantia nigra are particularly vulnerable to cell death in Parkinson’s disease (PD). One potential contributing factor is dysfunction of mitochondria, which are required for neuronal energy production and survival. We have identified a molecule that may control mitochondrial function in these neurons. This study aims to test whether this protein is required for neuronal survival and whether it can be used to protect neurons from cell death in PD.
To definitively test whether this particular protein is required for the survival of substantia nigra neurons, we will use pre-clinical models to delete this protein selectively from this type of neuron and evaluate neuronal loss and motor behavior. To determine whether enhancing activity through this pathway will prevent neuronal death, we will increase the amount of this protein in substantia nigra neurons of models undergoing cell death.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
This project has the potential to identify a biochemical pathway that can be targeted to prevent and/or slow the progression of neuronal cell loss in PD.
If we find that this particular molecule is useful in preventing neuronal death in a model of PD, we can work with our collaborators to design pharmacological approaches to enhance its activity and promote neuronal survival. Importantly, small molecules have been discovered that activate proteins with a similar structure, leading us to predict that drug development for this target is biologically feasible.