Molecular mechanisms of glutamate receptor-mediated excitotoxic neuronal cell death

Rita Sattler, Michael Tymianski

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)107-129
Number of pages23
JournalMolecular Neurobiology
Volume24
Issue number1-3
DOIs
StatePublished - Jan 1 2001

Keywords

  • Calcium
  • Glutamate receptor
  • Neurotoxicity
  • Postsynaptic density

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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