Prion diseases, or transmissible spongiform encephalopathies (TSEs), are a class of fatal neurodegenerative disorders that have acquired much public interest due to the epidemic of """"""""mad cow disease"""""""" in Britain and recent cases of transmission of this disease to humans. Although much is known about the disease process associated with the pathogenic isoform (PrPsc), the normal physiological function of the cellular prion protein (PrPc) has remained elusive. Much evidence has accumulated supporting a role for PrPc in the trafficking and metabolism of copper. In this proposal, the link between copper and PrPc will be further dissected through a structure-function analysis and examination of the copper-induced endocytic response of PrPc in post-mitotic neurons. Copper binding properties of a mutant of PrPc, known as PG14, will be measured to gain an understanding of the molecular basis behind the PG14-associated heritable form of Creutzfeldt-Jakob disease. Finally, a mouse model of an inheritable disease of copper metabolism (Menkes disease) will be used to determine whether PrPc plays a role in the maintenance of copper homeostasis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS046910-05
Application #
7266956
Study Section
Special Emphasis Panel (ZRG1-F03B (20))
Program Officer
Wong, May
Project Start
2003-08-01
Project End
2008-07-31
Budget Start
2007-08-01
Budget End
2008-07-31
Support Year
5
Fiscal Year
2007
Total Cost
$27,201
Indirect Cost
Name
Washington University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Christensen, Heather M; Harris, David A (2009) A deleted prion protein that is neurotoxic in vivo is localized normally in cultured cells. J Neurochem 108:44-56