Riluzole is the only drug approved for the treatment of amyotrophic lateral sclerosis (ALS) but its precise mode of action is not properly understood. Damage to axonal transport of neurofilaments is believed to be part of the pathogenic mechanism in ALS and this has been linked to defective glutamate handling and increased phosphorylation of neurofilament side-arm domains. Here, we show that riluzole protects against glutamate-induced slowing of neurofilament transport. Protection is associated with decreased neurofilament side-arm phosphorylation and inhibition of the activities of two neurofilament kinases, ERK and p38 that are activated in ALS. Thus, the anti-glutamatergic properties of riluzole include protection against glutamate-induced changes to neurofilament phosphorylation and transport.

Original languageEnglish
Pages (from-to)161-4
Number of pages4
JournalNeuroscience Letters
Issue number2
Publication statusPublished - 24 Apr 2009


  • Analysis of Variance
  • Animals
  • Axonal Transport/drug effects
  • Axons/drug effects
  • Brain/drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Antagonists/pharmacology
  • Extracellular Signal-Regulated MAP Kinases/metabolism
  • Glutamic Acid/toxicity
  • Immunohistochemistry
  • Neurofilament Proteins/metabolism
  • Neurons/drug effects
  • Neuroprotective Agents/pharmacology
  • Phosphorylation/drug effects
  • Rats
  • Riluzole/pharmacology
  • p38 Mitogen-Activated Protein Kinases/metabolism

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