In pre-clinical models, we identified an important role of cholinergic interneurons — which release the neurotransmitter acetylcholine — from part of the brain called the striatum in levodopa-induced dyskinesia. This small population of striatal neurons has not been well studied in Parkinson’s disease (PD) models and may present a new therapeutic target. Examining gene expression profiles in published data showed selective expression of molecules that can be targeted for therapeutic uses in nonparkinsonian models, providing a proof of principle to apply such approach for development of novel therapeutic targets for PD. We will carry out a similar approach for PD and dyskinesia models.
We hypothesize that selective gene expression profiles of striatal cholinergic interneurons in dyskinetic models will reveal molecular changes that can be targeted for therapy.
We will utilize a model to identify distinct gene expression profiles in this type of neuron. We will compare them in dyskinetic and non-dyskinetic, but parkinsonian, models, to identify different patterns for each state.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
The data obtained will provide an insight on specific molecular changes in striatal cholinergic neurons that may reveal potential targets for therapeutic manipulation.
Next Steps for Development:
Once we identify specific molecular changes in the striatal cholinergic neurons associated with dyskinesia, they will be targeted for therapy of dyskinesia.