This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Suppression of the lysosomal cysteine proteases have been identified in aging and various types of neuronal injuries. However, the role of the lysosomal proteases has not been investigated in Parkinson s Disease (PD). Recent in vitro studies have demonstrated an alternate programmed cell death pathway due to specific inhibition of cathepsin B resulting in an increased activity of the aspartate protease cathepsin D. Cystatin C is a potent endogenous inhibitor of the lysosomal cysteine proteases and has been identified in degenerating neurons with immunohistochemical analysis following injury. The objective of this project is to elucidate the potential relationship of cystatin C with the cysteine protease cathepsin B, and the aspartate protease cathepsin D using the experimental PD model of 6-hyroxydopamine toxicity. Thus, the proposed experiments examine and test the hypothesis that cystatin C contributes to cathepsin D induced neurodegeneration by suppressing cathepsin B in the dopaminergic neurons following 6-hydroxydopamine injection. This hypothesis will be tested in vitro with PC-12 cell cultures exposed to 6-hydroxydopamine toxicity and in vivo with 6-hydroxydopamine injections into the substantia nigra of rats. Co-localization of cystatin C with cathepsins B and D as well as quantitative changes in protein and messenger RNA and enzyme activity will be determined in injured neurons and PC-12 cells undergoing apoptosis. These findings are expected to increase the understanding of the complex cascade of biochemical events that ultimately leads to neuronal degeneration in PD.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Research Centers in Minority Institutions Award (G12)
Project #
5G12RR003020-23
Application #
7561439
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
2007-06-01
Project End
2008-05-31
Budget Start
2007-06-01
Budget End
2008-05-31
Support Year
23
Fiscal Year
2007
Total Cost
$57,180
Indirect Cost
Name
Florida Agricultural and Mechanical University
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
623751831
City
Tallahassee
State
FL
Country
United States
Zip Code
32307
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