Molecular mechanisms of glutamate receptor-mediated excitotoxic neuronal cell death |
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Authors: | Rita Sattler Michael Tymianski |
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Institution: | (1) Department of Neuroscience, Johns Hopkins University School of Medicine and Howard Hughes Medical Institute, 725 N Wolfe Street PCTB 904, 21209 Baltimore, MD, USA;(2) Division of Cellular and Molecular Neuroscience, Neuroprotection Laboratory, Toronto Western Hospital Research Institute, 11-416, 399 Bathurst Street, M5T 2S8 Toronto, ON, Canada |
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Abstract: | Excitotoxicity is one of the most extensively studied processes of neuronal cell death, and plays an important role in many
central nervous system (CNS) diseases, including CNS ischemia, trauma, and neurodegenerative disorders. First described by
Olney, excitotoxicity was later characterized as an excessive synaptic release of glutamate, which in turn activates postsynaptic
glutamate receptors. While almost every glutamate receptor subtype has been implicated in mediating excitotoxic cell death,
it is generally accepted that the N-methyl-D-aspartate (NMDA) subtypes play a major role, mainly owing to their high calcium
(Ca2+) permeability. However, other glutamate receptor subtypes such as 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionate
(AMPA) or kainate receptors have also been attributed a critical role in mediating excitotoxic neuronal cell death. Although
the molecular basis of glutamate toxicity is uncertain, there is general agreement that it is in large part Ca2+-dependent. The present review is aimed at summarizing the molecular mechanisms of NMDA receptor and AMPA/kainate receptor-mediated
excitotoxic neuronal cell death. |
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Keywords: | Neurotoxicity calcium glutamate receptor postsynaptic density |
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