Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways
- G. Hardingham, Y. Fukunaga, H. Bading
- BiologyNature Neuroscience
- 1 May 2002
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 neuron…
Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders
- G. Hardingham, H. Bading
- BiologyNature Reviews Neuroscience
- 1 October 2010
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.
Nuclear calcium signaling controls CREB-mediated gene expression triggered by synaptic activity
- G. Hardingham, Fiona J. L. Arnold, H. Bading
- BiologyNature Neuroscience
- 1 March 2001
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.
Distinct functions of nuclear and cytoplasmic calcium in the control of gene expression
- G. Hardingham, S. Chawla, C. Johnson, H. Bading
- BiologyNature
- 16 January 1997
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.
The Yin and Yang of NMDA receptor signalling
- G. Hardingham, H. Bading
- BiologyTrends in Neurosciences
- 1 February 2003
Mutant induced pluripotent stem cell lines recapitulate aspects of TDP-43 proteinopathies and reveal cell-specific vulnerability
- B. Bilican, A. Serio, S. Chandran
- BiologyProceedings of the National Academy of Sciences…
- 26 March 2012
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.
Synaptic NMDA receptor activity boosts intrinsic antioxidant defenses
- S. Papadia, Francesc X. Soriano, G. Hardingham
- BiologyNature Neuroscience
- 1 April 2008
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.
CBP: a signal-regulated transcriptional coactivator controlled by nuclear calcium and CaM kinase IV.
- S. Chawla, G. Hardingham, D. R. Quinn, H. Bading
- BiologyScience
- 4 September 1998
CBP was found to contain a signal-regulated transcriptional activation domain that is controlled by nuclear calcium and calcium/calmodulin-dependent (CaM) protein kinase IV and by cAMP, and this work defines a regulatory role fornuclear calcium and cAMP in CBP-dependent gene expression.
A calcium microdomain near NMDA receptors: on switch for ERK-dependent synapse-to-nucleus communication
- G. Hardingham, Fiona J. L. Arnold, H. Bading
- BiologyNature Neuroscience
- 1 June 2001
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.
Nuclear Ca2+ and the cAMP Response Element-Binding Protein Family Mediate a Late Phase of Activity-Dependent Neuroprotection
- S. Papadia, Patrick Stevenson, N. Hardingham, H. Bading, G. Hardingham
- BiologyJournal of Neuroscience
- 27 April 2005
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.
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