On the Hypes and Falls in Neuroprotection: Targeting the NMDA Receptor

Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen-Nürnberg

^* To whom correspondence should be addressed. E-mail: cmb{at}biochem.uni-erlangen.de.

	Abstract

Activation of the NMDA (N-methyl-D-aspartate) responsive subclass of glutamate receptors is an important mechanism of excitatory synaptic transmission. Moreover, NMDA receptors are widely involved in many forms of synaptic plasticity such as long-term potentiation (LTP) and long-term depression (LTD), which are thought to underlie complex tasks, including learning and memory. Dysfunction of these ligand-gated cation channels has been identified as an underlying molecular mechanism in neurological disorders ranging from acute stroke to chronic neurodegeneration in amyotrophic lateral sclerosis. Excessive glutamate levels have been detected following brain trauma and cerebral ischemia, resulting in an unregulated stimulation of NMDA receptors. These conditions are thought to elicit a cascade of excitation-mediated neuronal damage where massive increases in intracellular calcium concentrations finally trigger neuronal damage and apoptosis. Consistent with the hypothesis of NMDA receptors as essential mediators of excitotoxicity, the different functional domains of these ion channels have been identified as potential targets for neuroprotective agents. Following an initial hype on potential NMDA receptor therapeutics, the authors currently see a period of skepticism that, in reverse, appears to neglect the therapeutic potential of this receptor class. This review attempts a reappraisal of this important class of neurotransmitter receptors, with a focus on NMDA receptor heterogeneity, ligand binding domains, and candidate diseases for a potential neuroprotective therapy. NEUROSCIENTIST XX(X):xx–xx, XXXX. DOI: 10.1177/1073858406296259

First published on October 2, 2007, doi:10.1177/1073858406296259

The Neuroscientist 2007;13:594.

A more recent version of this article appeared on December 1, 2007


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				C. Beste, C. Saft, O. Gunturkun, and M. Falkenstein Increased Cognitive Functioning in Symptomatic Huntington's Disease As Revealed by Behavioral and Event-Related Potential Indices of Auditory Sensory Memory and Attention J. Neurosci., November 5, 2008; 28(45): 11695 - 11702. [Abstract] [Full Text] [PDF]

				D. M. Hermann Review: Future perspectives for brain pharmacotherapies: implications of drug transport processes at the blood--brain barrier Therapeutic Advances in Neurological Disorders, November 1, 2008; 1(3): 167 - 179. [Abstract] [PDF]

				A. D. Steele All quiet on the neuronal front: NMDA receptor inhibition by prion protein J. Cell Biol., October 14, 2008; 181(3): 407 - 409. [Abstract] [Full Text] [PDF]

				S. Ellefsen, G. K. Sandvik, H. K. Larsen, K.-O. Stenslokken, D. A. S. Hov, T. A. Kristensen, and G. E. Nilsson Expression of genes involved in excitatory neurotransmission in anoxic crucian carp (Carassius carassius) brain Physiol Genomics, September 17, 2008; 35(1): 5 - 17. [Abstract] [Full Text] [PDF]