Parkinson's disease (PD) is a neurological disorder characterized by the degeneration of nigrostriatal dopaminergic neurons. The cause of this degeneration has yet to be fully understood. However, there is increasing evidence that PD is the result of a complex set of interactions encompassing genetic predisposition, the innate oxidative characteristics of the nigrostriatal dopaminergic pathway and inflammation. Less than 10% of PD cases are hereditary. A subset of which has been linked to two mutations in the alpha-synuclein gene. Our laboratory has obtained a mouse that over-expresses human alpha-synuclein under the control of the platelet-derived growth factor promoter. Using this mouse as a genetic model of PD, I plan to examine the inflammatory mechanisms leading to the loss of nigrostriatal dopaminergic neurons after exposure to the inflammagen lipopolysaccharide (LPS). I hypothesize that in the context of increased alpha-synuclein expression, inflammation is detrimental to dopaminergic neurons. Furthermore, I hypothesize that LPS mediated inflammation will result in the loss of dopaminergic cells in the substantia nigra of the alpha-synuclein over-expressing murine model of PD. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31NS051163-01
Application #
6893196
Study Section
Special Emphasis Panel (ZRG1-BDCN-A (29))
Program Officer
Refolo, Lorenzo
Project Start
2005-08-01
Project End
2008-07-31
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
1
Fiscal Year
2004
Total Cost
$28,513
Indirect Cost
Name
University of California Los Angeles
Department
Neurology
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095