Grant: Operating Grant

The molecular mechanisms behind many neurodegenerative diseases are currently not well described. One example is multiple sclerosis (MS), where cellular stress can lead to brain inflammation. Following this, the immune system can then cause death of brain tissue. Our research, publicly available protein profiles and mouse models of brain inflammation have identified the protein Rab32 as a marker of this disease. This suggests that elevated levels of Rab32 are either intended to protect the brain upon an inflammatory insult or could actually boost the loss of critical brain functions. Interestingly, published and preliminary results from our laboratory show that Rab32 serves as a decision maker for the survival and function of mitochondria. These cellular power plants not only keep neurons alive, but also determine neuronal metabolism and inflammation. Therefore, Rab32 can pivotally extend or shorten neuronal life span, accelerate or slow down metabolism, and boost or inhibit inflammation. Together, these findings lead us to hypothesize that high levels of Rab32 could critically determine the outcome of the MS neurodegenerative syndrome. We will test our hypothesis by analyzing the consequences of elevated Rab32 in tissue culture models, neurons and animals. We will focus in particular on the interaction of Rab32 with a protein that is required for the proper functioning of mitochondria called dynamin related protein 1 (Drp1). This will answer whether Rab32 promotes neuroinflammatory pathologies or whether it is part of a protective response.