The Yin and Yang of NMDA receptor signalling

@article{Hardingham2003TheYA,
  title={The Yin and Yang of NMDA receptor signalling},
  author={Giles E. Hardingham and Hilmar Bading},
  journal={Trends in Neurosciences},
  year={2003},
  volume={26},
  pages={81-89}
}
Pro-survival signalling from the NMDA receptor.
TLDR
Ca2+ influx through the NMDA (N-methyl-D-aspartate) subtype of ionotropic glutamate receptors plays a Jekyll and Hyde role in the mammalian central nervous system and understanding the mechanisms that underlie these opposing effects may lead to strategies to selectively block pro-death signalling.
The Dichotomy of NMDA Receptor Signaling
  • S. Papadia, G. Hardingham
  • Biology
    The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry
  • 2007
TLDR
There is a growing understanding of the signaling events that mediate the opposing effects of NMDA-receptor activity and the factors that determine whether an episode ofNMDA- receptor activity will promote survival or death, which may lead to therapeutic strategies that enable the selective blockade of prodeath signaling cassettes while sparing physiological signaling to survival and plasticity.
Explorer The dichotomy of NMDA receptor signaling
TLDR
There is a growing understanding of the signalling events that mediate the opposing effects of NMda receptor activity, and the factors that determine whether an episode of NMDA receptor activity will promote survival or death, which may lead to therapeutic strategies that enable the selective blockade of pro-death signalling cassettes, while sparing physiological signalling to survival and plasticity.
Molecular Properties and Cell Biology of the NMDA Receptor
NMDA receptors (NMDARs) play a distinct role at excitatory glutamatergic synapses, where they are usually localized with other ionotropic glutamate receptors, including tors. Two features are
Coupling of the NMDA receptor to neuroprotective and neurodestructive events.
TLDR
Increased understanding in this field is leading to the discovery of new therapeutic targets and strategies for excitotoxic disorders, as well as a growing appreciation of the harmful consequences of NMDA receptor blockade.
Compartmentalized NMDA receptor signalling to survival and death
The ability of Ca2+ influx through the N‐methyl d‐aspartate subclass of glutamate receptor (NMDA receptor) to both kill neurons and to promote survival under different circumstances is well
Assembly and forward trafficking of NMDA receptors (Review)
TLDR
The current understanding of the mechanisms of NMDA receptor assembly is reviewed, how this assembly is regulated and how assembled receptors are trafficked to their appropriate sites in post-synaptic membranes where they are integral components of a macromolecular signalling complex are reviewed.
Extrasynaptic NMDA receptors : mediators of excitotoxic cell
TLDR
As extrasynaptic NMDA receptors are thought to be activated following hypoxic/ischemic insults, specific blockade of ExtrasynapticNMDA receptors or their signaling complex may efficiently reduce neuron loss following stroke.
Extrasynaptic NMDA receptors: mediators of excitotoxic cell death
TLDR
As extrasynaptic NMDA receptors are thought to be activated following hypoxic/ischemic insults, specific blockade of ExtrasynapticNMDA receptors or its signaling complex may efficiently reduce neuron loss following stroke.
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References

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TLDR
In cultured cortical neurons, suppressing the expression of the N MDAR scaffolding protein PSD-95 selectively attenuated excitotoxicity triggered via NMDARs, but not by other glutamate or calcium ion (Ca2+) channels.
Stimulation of protein tyrosine phosphorylation by NMDA receptor activation
TLDR
Stimulation of cultured rat hippocampal cells with glutamate resulted in the rapid and transient tyrosine phosphorylation of a 39-kilodalton protein (p39), which was found to be highly related or identical to the microtubule-associated protein 2 kinase, and the NMDA receptor signal may be processed by a sequential activation of protein kinases.
Treatment of Ischemic Brain Damage by Perturbing NMDA Receptor- PSD-95 Protein Interactions
N-methyl-d-aspartate receptors (NMDARs) mediate ischemic brain damage but also mediate essential neuronal excitation. To treat stroke without blocking NMDARs, we transduced neurons with peptides that
The Quantity of Calcium that Appears to Induce Neuronal Death
TLDR
It is shown that the absolute amount of 45Ca2+ taken up via the NMDA receptor correlates quantitatively with the amount of acute cell death in cultured cerebellar granule cells of the rat.
CREB Signaling-Timing Is Everything
TLDR
Some of the opposing models for how gene transcription in response to neuronal activity and elevations in intracellular calcium concentration is regulated appear to converge on cyclic AMP response element-binding (CREB) protein, with the mitogen-activated protein kinase pathways playing an important role.
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TLDR
Blockade of N-methyl-D-aspartate (NMDA) glutamate receptors for only a few hours during late fetal or early neonatal life triggered widespread apoptotic neurodegeneration in the developing rat brain, suggesting that the excitatory neurotransmitter glutamate, acting at NMDA receptors, controls neuronal survival.
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TLDR
A calcium pool in the immediate vicinity of synaptic NMDA receptors is the on switch for extracellular signal-regulated kinase (ERK1/2)-mediated synapse-to-nucleus signaling; this signal propagates to the nucleus independently of global increases in calcium concentration, stimulates SRE-dependent gene expression and prolongs the transcriptionally active state of CREB following brief synaptic stimuli.
Glutamate-induced neuron death requires mitochondrial calcium uptake
TLDR
Results indicate that very high levels of cytoplasmic calcium are not necessarily toxic to forebrain neurons, and that potential-driven uptake of calcium into mitochondria is required to trigger NMDA-receptor-stimulated neuronal death.
Glutamate release in severe brain ischaemia is mainly by reversed uptake
TLDR
It is demonstrated that transporter-mediated glutamate homeostasis fails dramatically in ischaemia: instead of removing extracellular glutamate to protect neurons, transporters release glutamate, triggering neuronal death.
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