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

Research output: Contribution to journalArticle

Abstract

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
Volume1832
Issue number2
DOIs
Publication statusPublished - Feb 2013

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine

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