NMDA receptor signaling: death or survival?

Glutamate-induced neuronal damage is mainly caused by overactivation of N-methyl-D-aspartate (NMDA) receptors. Conversely, normal physiological brain function and neuronal survival require adequate activation of NMDA receptors. Studies have revealed that NMDA receptor-induced neuronal death or survival is mediated through distinct subset of NMDA receptors triggering different intracellular signaling pathways. Here we discuss recent advances in the characterization of NMDA receptors in neuronal protection, emphasizing subunit-specific role, which contributes to temporal-spatial distribution, subcellular localization and diverse channel properties of NMDA receptors.