Study Rationale: NOD2 is a signaling protein which has been found to be more abundant and more active in brain tissues of patients with Parkinson’s disease. Certain changes in the sequence encoding NOD2 have also been linked to an increased risk of developing PD. It is currently not understood how NOD2 functions in PD and whether too much or too little NOD2 activity is harmful or beneficial. Currently, NOD2 is known to have both protective and harmful roles in disease.
Hypothesis: This study seeks to understand how having too much or too little NOD2 activity, or having a genetic change in the NOD2 gene, influences the function of microglia and T cells, two cell types important in the disease progression in PD.
Study Design: We propose to use a combination of genetic data and functional assays using tissues from healthy individuals, individuals with PD and individuals with PD who have a specific change in their NOD2 gene, to determine how NOD2 influences specific functions of microglia and T cells to cause or protect against disease. In some cases, we also propose to use cell lines which we can genetically manipulate to ask the same questions.
Impact on Diagnosis/Treatment of Parkinson’s disease: Understanding how NOD2 functions in healthy individuals and in people with PD will determine if targeting this protein (maybe in a cell type specific way) is likely to be beneficial in the setting of PD.
Next Steps for Development: Identifying how NOD2 impacts the function of microglia and T cells will help in the development of therapies which reduce the harmful effects of too much NOD2 activity but preserve or enhance the beneficial effects of signaling through this receptor.