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Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways
Here we report that synaptic and extrasynaptic NMDA (N-methyl-D-aspartate) receptors have opposite effects on CREB (cAMP response element binding protein) function, gene regulation and neuronExpand
Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders
Perturbations in the balance between synaptic and extrasynaptic NMDAR activity contribute to neuronal dysfunction in acute ischaemia and Huntington's disease, and could be a common theme in the aetiology of neurodegenerative diseases. Expand
Nuclear calcium signaling controls CREB-mediated gene expression triggered by synaptic activity
In hippocampal neurons, signaling to CREB can be activated by nuclear calcium alone and does not require import of cytoplasmic proteins into the nucleus, which is critical for CREB-mediated transcription by synaptic NMDA receptors. Expand
Distinct functions of nuclear and cytoplasmic calcium in the control of gene expression
It is shown that gene expression is differentially controlled by nuclear and cytoplasmic calcium signals which enable a single second messenger to generate diverse transcriptional responses. Expand
The Yin and Yang of NMDA receptor signalling
Ca(2+) entry through the NMDA subtype of glutamate receptors has the power to determine whether neurons survive or die, and the mechanisms behind this dichotomous signalling are understood. Expand
Mutant induced pluripotent stem cell lines recapitulate aspects of TDP-43 proteinopathies and reveal cell-specific vulnerability
It is concluded that expression of physiological levels of TDP-43 in human neurons is sufficient to reveal a mutation-specific cell-autonomous phenotype and strongly supports this approach for the study of disease mechanisms and for drug screening. Expand
Synaptic NMDA receptor activity boosts intrinsic antioxidant defenses
It is found that in rat neurons, synaptic activity, acting via NMDA receptor (NMDAR) signaling, boosted antioxidant defenses by making changes to the thioredoxin-peroxiredoxin system by influencing the progression of pathological processes associated with oxidative damage. Expand
Nuclear Ca2+ and the cAMP Response Element-Binding Protein Family Mediate a Late Phase of Activity-Dependent Neuroprotection
It is shown that that an episode of synaptic activity can promote neuroprotection for a long time after that activity has ceased, and activity-dependent neuroprotection comprises two mechanistically distinct phases that differ in their spatial requirements for calcium and in their reliance on the CREB family. Expand
Coupling of the NMDA receptor to neuroprotective and neurodestructive events.
  • G. Hardingham
  • Biology, Medicine
  • Biochemical Society transactions
  • 1 December 2009
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. Expand
Coupling of extrasynaptic NMDA receptors to a CREB shut-off pathway is developmentally regulated.
It is found that synaptic NMDAR activity induced CREB phosphorylation at day in vitro (DIV) 7 and DIV 12 and the extrasynaptic NMDar-dependent CREB shut-off signal is developmentally regulated. Expand