The present proposal seeks to clarify the role of aberrant Cu chemistry (peroxidation/nitration) in the pathogenesis of SOD1. One component will examine the abilities of FALS mutant SOD1, particularly enzyme with mutations involving crucial histidine, to bind Cu and to react with H202 and -OONO. A second components will determine whether experimentally mutated SOD1, lacking the capacity to bind Cu and encoding FALS mutations, can cause ALS-like motor neuron disease in mice. The third component of the study will operate under the assumption that, even if aberrant Cu chemistry is not the primary mechanism by which all FALS mutant SOD1 causes disease, some mutants do have enhanced peroxidase and nitration activities, and the level of these associated activities may modulate the severity of the disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS037225-01
Application #
2488310
Study Section
Special Emphasis Panel (ZRG1-NLS-3 (01))
Program Officer
Kerza-Kwiatecki, a P
Project Start
1998-04-01
Project End
2001-03-31
Budget Start
1998-04-01
Budget End
1999-03-31
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Pathology
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218