Funded Studies
Objective/Rationale:
People with mutations in the Parkin gene can develop young-onset Parkinson’s disease (PD). The protein parkin (genes encode proteins) modifies the structure of many other cell proteins. Recent studies show that multiple proteins regulating immune function are modified by parkin. We propose that disruption in the immune proteins in brain cells of people with Parkin mutations impairs their ability to repair the dopamine neurons damaged in PD.
Project Description:
Pre-clinical models with and without the parkin protein will be introduced a toxin into the brain region that becomes damaged during Parkinson’s disease. The response of the brain’s immune cells to this stress will be determined. The microglial cells will then be modified in a culture dish to evaluate whether the replacement of the immune system that is not functioning in the parkin-depleted cells can rescue their immune response. To test whether these immune changes are operational in humans, we will compare immune cells people with Parkin mutations to individuals with intact Parkin function.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
If our hypothesis is proven, these findings could lead to approaches to modify the immune system as a way to either prevent PD or to slow its progression. This would have the potential to open up a completely new therapeutic approach.
Anticipated Outcome:
This study should allow us to test the hypothesis that an important function of the protein parkin is to facilitate the brain immune system to repair neuronal cells that are normally damaged. If proven correct, this study could be expanded upon to test this concept in greater detail in cells and possibly from spinal fluid in patients with mutations in Parkin and young-onset Parkinson’s disease.