The etiology of certain acute insults and chronic neuro-degenerative disorders has been advanced by the finding that these diseases are possibly manifested fully or in part through glutamate receptor activation. These diseases include stroke, Alzheimer's and Huntington's disease. Unfortunately, very little is known about the intracellular mechanisms responsible for glutamate-induced cell death. The power of molecular genetics will be used to probe signal transduction mechanisms. The catalytic or regulatory (inhibitory) domain of protein kinase C, calcium/calmodulin-dependent protein kinase II, and calcium activated neutral proteinase will be expressed in cultured neurons using a HSV-1 vector system. Infected cells will then be challenged with toxic doses of various glutamate agonists to determine the role of these enzymes in mediating neuronal death. The development of the HSV-1 vector system to study glutamate neurotoxicity could have broad implications: 1) An understanding of these intracellular processes may suggest clinical therapeutic strategies for stroke. 2) The HSV-1 vector may provide a novel therapeutic approach in treating chronic neurologic disorders by restoring function through gene therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32MH009823-05
Application #
2241119
Study Section
Neurosciences Research Review Committee (BPN)
Project Start
1993-04-01
Project End
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
5
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115