Characterization of LRRK2 Cellular and Signaling Pathways

Promising Outcomes of Original Grant:
In the original funded grant, we propose to identify LRRK2 substrates using a chemical genetics approach. We have developed suitable methods and key reagents that will be used to identify and validate candidate LRRK2 substrates. The interim results obtained thus far suggest that our original project should proceed as planned. 

Objectives for Supplemental Investigation: 
In this supplemental proposal, we plan to conduct genome-wide screens for modifying genes of LRRK2-linked neuronal phenotype in a C. elegans model.  This supplemental project differs from the original grant in that it uses a genetic model to identify molecular components involved in the cellular signaling mediated by LRRK2.  On the other hand, this supplemental project will complement the original grant by expanding the search for LRRK2 effectors and interacting proteins that make up the LRRK2 signaling pathways. 

Importance of This Research for the Development of a New PD Therapy:
Identification and elucidation of molecular pathways leading to LRRK2-mediated PD pathogenesis may lead to the discovery of novel therapeutic targets. As a result, potential drugs or other methods of intervention may be developed for PD.