Study Rationale: Brain inflammation has been associated with the development of Parkinson’s disease (PD). In search for factors that may influence inflammation that triggers PD, several groups have identified a putative role for a protein named NOD2. NOD2 was previously known for controlling inflammation in response to bacteria in the gut.
Hypothesis:BIn this project, we aim to directly assess the role played by NOD2 in murine models of PD.
Study Design:BWe will use mice that are deficient for the gene encoding NOD2 (=Nod2-/- mice), and leverage two well-characterized PD models in mice in which the pathogenic form of a-synuclein, a driver of PD, is delivered directly into the striatum of the mice. Following this injection, animals will experience or not a treatment of intestinal inflammation. The animals will be assessed for behavioral deficits and brains will be collected for biochemical assays specifically targeted towards the analysis of PD phenotypes.
Impact on Diagnosis/Treatment of Parkinson’s disease: If the role of NOD2 in PD pathophysiology is confirmed, this may offer new therapeutic opportunities focused on targeting NOD2 function. Moreover, this would provide novel insights regarding the potential link between intestinal inflammation, gut microbes, and PD.
Next Steps for Development: If successful, the next steps may be to test NOD2 antagonists delivered into the brain or to modulate the intestinal microbiota to limit the translocation of bacteria-derived molecules that activate NOD2.