Grant: Project Grant

Parkinson's disease (PD) is a devastating neurodegenerative disorder which leads to loss of special brain cells which produce the neurochemical signal dopamine. How these brain cells die and lead to the symptoms of PD is not known. These symptoms include rigidity, tremors, and slowness of movement. Recently, there have been a number of genes identified that are now known to cause PD. However, the reason why mutations in these genes lead to PD is unknown and one of the most urgent questions in the field. Our lab has generated new insights into how two of these genes, Pink1 and Lrrk2 may cause PD. For example, we have growing evidence that Pink1 regulates the health of the power generators of the cell, mitochondria. We also show that the PD gene Lrrk2 affects immune cell function, which we suspect is overactivated, and leads to brain cell damage. In this project, we will determine how these new pathways work and more importantly, whether they are central to the degenerative process in PD. We will also generate ways to control these pathways using drugs that have already been approved for human use. In this way, we hope to not only understand the fundamentals of degeneration in PD, but also develop therapeutic strategies that can be immediately tested in patients.