Role of the N-methyl-d-aspartate receptors complex in amyotrophic lateral sclerosis

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Amyotrophic lateral sclerosis (ALS) is an adult onset neurodegenerative disease pathologically characterized by the massive loss of motor neurons in the spinal cord, brain stem and cerebral cortex. There is a consensus in the field that ALS is a multifactorial pathology and a number of possible mechanisms have been suggested. Among the proposed hypothesis, glutamate toxicity has been one of the most investigated. Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor mediated cell death and impairment of the glutamate-transport system have been suggested to play a central role in the glutamate-mediated motor neuron degeneration. In this context, the role played by the N-methyl-d-aspartate (NMDA) receptor has received considerable less attention notwithstanding its high Ca2+ permeability, expression in motor neurons and its importance in excitotoxicity. This review overviews the critical role of NMDA-mediated toxicity in ALS, with a particular emphasis on the endogenous modulators of the NMDAR.

Original languageEnglish
Pages (from-to)312-322
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Issue number2
Publication statusPublished - Feb 2013


  • Amyotrophic lateral sclerosis
  • Excitotoxicity
  • Glutamate
  • N-methyl-d-aspartate receptor
  • Neurodegeneration

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine


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