TY  - GEN
Y1  - 2004///
SP  - 253
TI  - Extrasynaptic NMDA Receptors : Mediators of Excitotoxic Cell Death
EP  - 266
CY  - Stuttgart
A1  - Wittmann, Malte
A1  - Bengtson, C. Peter
A1  - Bading, Hilmar
PB  - Medpharm Scientific Publishers
AV  - public
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/5390/
KW  - NMDA receptor 
KW  -  calcium signaling 
KW  -  survival 
KW  -  cell death 
KW  -  CREB 
KW  -  stroke
ID  - heidok5390
N2  - The N-methyl-D-aspartate (NMDA) type of glutamate receptor is a calcium-permeable ion channel with important functions in the physiology and pathology of the mammalian brain. NMDA receptors are critical for long-lasting, activity-induced changes in synaptic transmission, a process thought to be involved in learning and memory. NMDA receptors also control neuronal survival and cell death. How can the biological consequences of NMDA receptor activation be so diametrically opposed? The outcome of NMDA receptor activation appears to be determined by its localization. Stimulation of synaptic NMDA receptors (by synaptically-released glutamate) activates gene expression mediated by the transcription factor, cAMP-response element-binding-protein (CREB) and induces pro-survival events. In contrast, calcium flux through extrasynaptic NMDA receptors overrides these functions, shutting off CREB activity, and causing mitochondrial dysfunction and cell death. These differences in the biological response are likely due to differences in the intracellular signaling complexes associated with synaptic vs. extrasynaptic NMDA receptors. As extrasynaptic NMDA receptors are thought to be activated following hypoxic/ischemic insults, specific blockade of extrasynaptic NMDA receptors or its signaling complex may efficiently reduce neuron loss following stroke.
ER  -