Inherited mutations in a gene called LRRK2 have been found to cause Parkinson ’s disease. The LRRK2 gene encodes an enzyme called a kinase, for which no exact function has been elucidated to date. It is crucial to discover the role of LRRK2 in the brain because it is a good candidate for drug therapy for Parkinson’s disease. We seek to determine what controls LRRK2 function as well as what processes LRRK2 controls.
We will seek to discover the LRRK2 signaling cascade. We will perform biochemical and genetic experiments to define the players that make up the cellular processes that regulate LRRK2. We will take steps to elucidate the processes that LRRK2 controls. Since LRRK2 is a good candidate for drug therapy, there is a need to be able to assess the effectiveness of LRRK2 based treatments in a non-invasive manner; we will work toward developing this assay. We will employ genetic, biochemical and cell biological techniques to achieve these goals.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
The successful outcome of our work will yield insight into the role of LRRK2 in Parkinson’s disease and define pathways in which it is involved. This will facilitate the development of novel therapeutics as well as being able to test their effectiveness in patients.
At the end of this project we will have defined inputs that regulate LRRK2 as well as the downstream targets of LRRK2. We hope to develop an understanding of the how PD associated mutations affect those inputs and downstream outputs related to LRRK2 activities. Finally, we will have a good understanding of how to assay LRRK2 activity in PD patient derived samples.