Study Rationale:
Parkinson's disease (PD) is caused by death of dopamine-containing cells in the brain. We discovered that a protein known as RGS6 is expressed in these cells in pre-clinical models of PD and functions to prevent their death during aging and in response to toxins that cause PD. RGS6 is also expressed in these same neurons in humans and is lost in people with PD. Together these findings indicate that RGS6 loss may cause death of the neurons responsible for PD.
Hypothesis:
We hypothesize that RGS6 is a critical neuroprotective protein that neurotoxin-induced death of neurons responsible for PD.
Study Design:
Our proposed studies will determine how RGS6 is lost in the brains of people with PD. We will ask whether loss of RGS6 is due to differences in the sequence (blueprint) of the RGS6 gene, in the activity or regulation of this gene or in the stability of the RGS6 protein.
Impact on Diagnosis/Treatment of Parkinson's Disease:
Identifying a genetic basis for RGS6 loss could lead to development of RGS6-based genetic screening to diagnose individuals susceptible to developing PD. Identifying the basis for RGS6 loss could also lead to novel RGS6-based therapies for Parkinson's.
Next Steps for Development:
RGS6-based diagnostic or predictive genetic testing would require additional large-scale screens. RGS6-based therapies would require development and testing of drugs or virally-delivered genes that prevent RGS6 loss in pre-clinical models prior to testing in humans. The present study could lead to novel ways to identify and treat Parkinson's-related neuronal cell death.