Study Rationale: The NOD2 protein plays a key role in how the immune system detects bacteria and protects the gut. Recent research suggests that genetic variation in the NOD2 gene may be linked to Parkinson’s disease (PD), possibly by contributing to brain inflammation or affecting how nerve cells function. However, we still do not fully understand what mechanisms these genetic changes affect in the body or how they influence PD risk. By exploring the role of NOD2 in the brain, gut and immune system, we hope to uncover new clues about what causes PD and identify potential novel targets for treatment.
Hypothesis: We believe that specific changes in the NOD2 gene or other genes that interact with NOD2, influence the risk of PD by altering gene expression and immune system activity in the brain and body.
Study Design: We will study the effect of genetic changes in the NOD2 and other related genes on developing PD by analyzing large collections of biological samples from diverse individuals. We will characterize how these changes affect expression and activity of NOD2 and additional genes that interact with NOD2 in different tissues, including the brain, gut and immune cells. We will also compare NOD2-related effects in PD to those in other diseases like inflammatory bowel disease to identify shared patterns and risk factors. Our goal is to pinpoint which gene changes within the NOD2 pathway are most important in driving PD.
Impact on Diagnosis/Treatment of Parkinson’s disease: This study could advance our understanding of how genetic variation in NOD2 drives the risk for PD and uncover biological pathways that could be targeted by future therapies.
Next Steps for Development: If successful, we will work to validate our findings in additional patient groups and begin testing whether targeting NOD2-related pathways could help slow or prevent the development of PD.