Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders.

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Bibliographic Details
Title:	Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders.
Authors:	Hardingham, Giles E., Bading, Hilmar
Source:	Nature Reviews Neuroscience. Oct2010, Vol. 11 Issue 10, p682-696. 15p. 1 Black and White Photograph, 6 Diagrams.
Subjects:	Methyl aspartate, Neurodegeneration, Neural receptors, Neural stimulation, Cell death, Etiology of diseases, Animal experimentation, Cell receptors, Cellular signal transduction, Comparative studies, Gene expression, Research methodology, Medical cooperation, Nervous system, Research, Oxidative stress, Evaluation research, Neuroprotective agents
Abstract:	There is a long-standing paradox that NMDA (N-methyl-D-aspartate) receptors (NMDARs) can both promote neuronal health and kill neurons. Recent studies show that NMDAR-induced responses depend on the receptor location: stimulation of synaptic NMDARs, acting primarily through nuclear Ca(2+) signalling, leads to the build-up of a neuroprotective 'shield', whereas stimulation of extrasynaptic NMDARs promotes cell death. These differences result from the activation of distinct genomic programmes and from opposing actions on intracellular signalling pathways. 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. Neuroprotective therapies should aim to both enhance the effect of synaptic activity and disrupt extrasynaptic NMDAR-dependent death signalling. [ABSTRACT FROM AUTHOR]
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Database:	Psychology and Behavioral Sciences Collection

Description
Abstract:	There is a long-standing paradox that NMDA (N-methyl-D-aspartate) receptors (NMDARs) can both promote neuronal health and kill neurons. Recent studies show that NMDAR-induced responses depend on the receptor location: stimulation of synaptic NMDARs, acting primarily through nuclear Ca(2+) signalling, leads to the build-up of a neuroprotective 'shield', whereas stimulation of extrasynaptic NMDARs promotes cell death. These differences result from the activation of distinct genomic programmes and from opposing actions on intracellular signalling pathways. 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. Neuroprotective therapies should aim to both enhance the effect of synaptic activity and disrupt extrasynaptic NMDAR-dependent death signalling. [ABSTRACT FROM AUTHOR]
ISSN:	1471003X
DOI:	10.1038/nrn2911