Parkinson's disease is the second most common neurodegenerative disease in the US and it has no cure. Thanks to rapid advances in genetics, important molecular targets in the pathogenesis of Parkinson's disease have been identified. Mutations in the Leucine rich repeat kinase 2 (Lrrk2) are associated with an autosomal dominant form of Parkinson's. An understanding of the molecular regulation and cellular signaling pathways of Lrrk2 in dopaminergic neurons is a necessary in first step in determining whether Lrrk2 or its signaling partners might be exploited as therapeutic targets in the treatment of both familial and idiopathic Parkinson's disease. We plan to use cell biological, biochemical, and mass spectrometric techniques, complemented by molecular modeling, to: 1.) determine the mechanistic nature of the Lrrk2 kinase domain mutations found in Parkinson's disease; 2.) investigate the molecular mechanisms by which Lrrk2 kinase activity is regulated; and 3) Identify components of Lrrk2 signaling complexes. The proposed research will provide much needed insight into the critical nature of Lrrk2 in the development of Parkinson's disease and lay the groundwork for the development of targeted therapeutics for the treatment of Parkinson's disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21NS055699-02
Application #
7268123
Study Section
Special Emphasis Panel (ZNS1-SRB-G (04))
Program Officer
Sieber, Beth-Anne
Project Start
2006-07-15
Project End
2010-03-31
Budget Start
2007-07-01
Budget End
2010-03-31
Support Year
2
Fiscal Year
2007
Total Cost
$194,242
Indirect Cost
Name
Michigan State University
Department
Physiology
Type
Schools of Medicine
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824