The Role of Excitotoxicity in ALS--what Is the Evidence?

J Neurol. 2000 Mar;247 Suppl 1:I7-16. doi: 10.1007/s004150050552.

Abstract

It is well accepted that excitotoxic mechanisms contribute to the pathogenesis of acute neuronal death in stroke, epilepsy, or brain trauma. It is less widely acknowledged that excitotoxic mechanisms play a role in the pathogenesis of chronic neurological disorders, in particular neurodegenerative diseases. However, evidence is accumulating that this mechanism is indeed part of the pathogenesis of late-onset neurodegenerative diseases. One of the clinical examples may be amyotrophic lateral sclerosis, a disease in which antiexcitotoxic strategies have neuroprotective effects in both, an established animal model and in man. In addition, there is accumulating neuropathological, pathobiochemical and pathophysiological evidence which indicates that excitotoxic mechanisms are part of the pathogenesis of the human disease and consequently part of the mechanisms explaining selective vulnerability ("pathoclisis") in the human motor system.

Publication types

  • Review

MeSH terms

  • Amyotrophic Lateral Sclerosis / etiology*
  • Amyotrophic Lateral Sclerosis / pathology
  • Animals
  • Disease Models, Animal
  • Glutamic Acid / adverse effects
  • Glutamic Acid / metabolism
  • Humans
  • Hypoxia
  • Motor Neurons / pathology
  • Nerve Degeneration
  • Neurotoxins / adverse effects*
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1

Substances

  • Neurotoxins
  • SOD1 protein, human
  • Glutamic Acid
  • Superoxide Dismutase
  • Superoxide Dismutase-1