Molecular Neurobiology

, Volume 24, Issue 1, pp 107–129

Molecular mechanisms of glutamate receptor-mediated excitotoxic neuronal cell death

Article

DOI: 10.1385/MN:24:1-3:107

Cite this article as:
Sattler, R. & Tymianski, M. Mol Neurobiol (2001) 24: 107. doi:10.1385/MN:24:1-3:107

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.

Index Entries

Neurotoxicity calcium glutamate receptor postsynaptic density 

Copyright information

© Humana Press Inc 2001

Authors and Affiliations

  1. 1.Department of NeuroscienceJohns Hopkins University School of Medicine and Howard Hughes Medical InstituteBaltimoreUSA
  2. 2.Division of Cellular and Molecular Neuroscience, Neuroprotection LaboratoryToronto Western Hospital Research InstituteTorontoCanada

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