Riluzole protects against glutamate-induced slowing of neurofilament axonal transport.
Yates, Darran M
De Vos, Kurt J
Leigh, P Nigel
McLoughlin, Declan M
Miller, Christopher C J
AffiliationMRC Centre for Neurodegeneration Research, Institute of Psychiatry, King's College, London, UK.
MeSHAnalysis of Variance
Dose-Response Relationship, Drug
Excitatory Amino Acid Antagonists
Extracellular Signal-Regulated MAP Kinases
p38 Mitogen-Activated Protein Kinases
MetadataShow full item record
CitationRiluzole protects against glutamate-induced slowing of neurofilament axonal transport. 2009, 454 (2):161-4 Neurosci. Lett.
AbstractRiluzole 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.
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