Under normal circumstances, glutamate serves as a nurturing neural signal important for growth and plasticity, but in some disease states it can act as a lethal killer. A paper in the May issue of Nature Neuroscience sheds light on the molecular events that determine how and when signaling through the NMDA subtype of glutamate receptor crosses the line between life and death.
Hilmar Bading and colleagues provide evidence that a key determinant of the nature of NMDA receptor signaling is the location of the activated receptors. Growth- and survival-promoting signals derive from NMDA receptors at the synapses, the sites of communication between neurons in the brain. In contrast, a cell death–promoting signal emerges from NMDA receptors on the cell’s surface but outside of synapses. This death signal appears to attain dominance when both pathways are activated together, because it shuts off the gene regulation protein CREB that is turned on by synaptic NMDA receptors. Thus one exciting future challenge will be to develop safe and effective ways to block extrasynaptic, but not synaptic, NMDA receptors. Such tools may help prevent cell loss during stroke and perhaps also in neurodegenerative diseases like Alzheimer’s disease.
Dr. Hilmar Bading
Dept of Neurobiology
University of Heidelberg, Germany
Tel: +49 622 154 8218
Additional contact for comment on paper:
Dr. David Ginty
Dept of Neuroscience
Johns Hopkins University School of Medicine
Baltimore, MD, USA
Tel: +1 410 614 9494
Also available online.
(C) Nature Neuroscience press release.
Message posted by: Trevor M. D'Souza