Glutamate receptors, neurotoxicity and neurodegeneration

Pflugers Arch. 2010 Jul;460(2):525-42. doi: 10.1007/s00424-010-0809-1. Epub 2010 Mar 14.


Glutamate excitotoxicity is a hypothesis that states excessive glutamate causes neuronal dysfunction and degeneration. As glutamate is a major excitatory neurotransmitter in the central nervous system (CNS), the implications of glutamate excitotoxicity are many and far-reaching. Acute CNS insults such as ischaemia and traumatic brain injury have traditionally been the focus of excitotoxicity research. However, glutamate excitotoxicity has also been linked to chronic neurodegenerative disorders such as amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease and others. Despite the continued research into the mechanisms of excitotoxicity, there are currently no pharmacological interventions capable of providing significant neuroprotection in the clinical setting of brain ischaemia or injury. This review addresses the current state of excitotoxic research, focusing on the structure and physiology of glutamate receptors; molecular mechanisms underlying excitotoxic cell death pathways and their interactions with each other; the evidence for glutamate excitotoxicity in acute neurologic diseases; laboratory and clinical attempts at modulating excitotoxicity; and emerging targets for excitotoxicity research.

Publication types

  • Review

MeSH terms

  • Animals
  • Antioxidants / therapeutic use
  • Calcium / metabolism
  • Calpain / physiology
  • Caspases / physiology
  • Cell Death / physiology
  • Free Radical Scavengers / therapeutic use
  • Free Radicals / metabolism
  • Glutamic Acid / adverse effects*
  • Glutamic Acid / physiology
  • Humans
  • Hypothalamus / drug effects
  • Nerve Degeneration / physiopathology*
  • Neurodegenerative Diseases / physiopathology*
  • Neurotoxicity Syndromes / physiopathology*
  • Nitric Oxide / physiology
  • Receptors, AMPA / antagonists & inhibitors
  • Receptors, AMPA / physiology
  • Receptors, Glutamate / physiology*
  • Receptors, Kainic Acid
  • Receptors, Metabotropic Glutamate / physiology
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Sodium-Calcium Exchanger / therapeutic use
  • Zinc / physiology


  • Antioxidants
  • Free Radical Scavengers
  • Free Radicals
  • Receptors, AMPA
  • Receptors, Glutamate
  • Receptors, Kainic Acid
  • Receptors, Metabotropic Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • Sodium-Calcium Exchanger
  • Nitric Oxide
  • Glutamic Acid
  • Calpain
  • Caspases
  • Zinc
  • Calcium