Herin, Greta Ann
(2003)
STUDIES ON THE ROLE OF THE N-TERMINAL DOMAIN OF NR1 IN THE REDOX MODULATION OF NR2A-CONTAINING NMDA RECEPTORS.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
The NMDA receptor is the subject of intense study due to its critical role in many neuronal processes and neuropathologies. This receptor is modulated by a wide variety of endogenous and exogenous agents, including reducing and oxidizing (redox) agents. Despite a wealth of physiological information, details of the structural basis of modulation are only beginning to emerge. It has been proposed that the amino terminal domain (ATD) of NMDA receptor subunits may serve as a modulatory domain, as several agents appear to have sites of action in this region of the receptor. NR1/NR2A receptors contain cysteines in the ATD of both NR1 and NR2 that confer unique redox sensitivity to these receptors; however, the ATD redox sensitivity of NR1/NR2A receptors remains largely unexplored. The goal of this dissertation was to explore the impact of reducing and oxidizing agents on NMDA receptor function, focusing on the amino terminal domain redox sites. Here we demonstrate that a clinically efficacious neuroprotective agent, ebselen, is active as an oxidizing agent of the NMDA receptor. Additionally, these studies demonstrate a novel modulation of NR1/NR2A redox mutants by the polyamine spermine and explore a relationship between redox and spermine modulation of NR1/NR2A mutant receptors.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
8 December 2003 |
| Date Type: |
Completion |
| Defense Date: |
19 August 2003 |
| Approval Date: |
8 December 2003 |
| Submission Date: |
29 September 2003 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Neurobiology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
allosteric modulation; ebselen; glutamate receptors; ion channels; site-directed mutagenesis; spermine |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-09292003-021236/, etd-09292003-021236 |
| Date Deposited: |
10 Nov 2011 20:02 |
| Last Modified: |
15 Nov 2016 13:50 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/9407 |
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