NMDA redox site

NMDA receptors ( Figure 1.3-2) are the most complex of the ionotropic receptors. In addition to the recognition site for glutamate, NMDA receptors contain several allosteric modulatory sites, including (1) a site for the endogenous brain amino acids glycine and D-serine, (2) a polyamine-sensitive site, and (3) a redox site that is sensitive to glutathione (see Chapter 2.5 this volume). All sites act primarily to facilitate activity at the receptor. 

Aizenman E, Hartnett KA, Reynolds IJ Oxygen free radicals regulate NMDA receptor function via a redox modulatory site. Neuron 5 841—846, 1990... 

Sun, P., Rane, S. G., Gunasekar, P. G., Borowitz, J. L., Isom, G. E. (1999). Cyanide interaction with redox modulatory sites enhances NMDA receptor responses. Journal of Biochemical Molecular... 

Sucher, N. J., and Lipton, S. A. (1991). Redox modulatory site of the NMDA receptor-channel complex Regulation by oxidized glutathione. J. Neurosci. Res. 30, 582-591. 

Ascorbic acid has also been suggested to be neuroprotective by inhibiting NMDA receptor activity via a redox modulatory site on the receptor (Section 4). Theoretically, high levels of ascorbic acid in the central nervous system could be neuroprotective, as inhibition of the NMDA receptor protects neurons from ischemic damage (Simon et al., 1984). In fact, ascorbic acid protects against NMDA-mediated neurotoxicity in cortical cell cultures (Majewska and Bell, 1990), although the required concentration is relatively high (1-3 mM). 

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