Combating Parkinson’s disease by modulating the activity of the kinase LRKK2 by way of passive exercise and an evolutionary approach

Parkinson's disease (PD) is a neurodegenerative disease that affects seven to ten million people worldwide. Despite the extensive research, a cure for PD is still unavailable. Passive exercise by whole-body vibration (WBV) has shown to have positive effects on both the brain and muscular system, which makes it a potential treatment for PD. A major limitation for the use of WBV in PD is that the optimal intervention protocol remains to be determined. To provide a rational for an optimal protocol, the field needs to know first which underlying mechanism of PD is most sensitive to WBV. I propose that the leucine rich repeat kinase 2 (LRRK2) pathway should be the focus of research. LRRK2 plays an essential role in PD pathogenesis and recent data strongly suggest that LRRK2 mediates this role via the immune response. Interestingly, several studies have shown that the beneficial anti-inflammatory effects of WBV also involve the immune system.
In the current project we will characterize the cellular role of LRRK2 and the molecular effect of WBV on LRRK2-mediated signaling and PD in general. For this I want to combine molecular characterization with the power of evolution. We will use cellular models from all kingdoms of life, as well an animal model.
Studying LRRK2 signaling across some animal taxa will shed light on its evolutionary context. The evolutionary perspective in view of the effect of WBV will contribute to the concept of evolutionary medicine.