4.4 Article

Riluzole protects against glutamate-induced slowing of neurofilament axonal transport

Journal

NEUROSCIENCE LETTERS
Volume 454, Issue 2, Pages 161-164

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2009.02.061

Keywords

Amyotrophic lateral sclerosis; Motor neuron disease; Extracellular-regulated kinase; p38; Neurofilament; Axonal transport

Categories

Funding

  1. Motor Neurone Disease Association
  2. MRC
  3. Wellcome Trust
  4. Alzheimer's Society
  5. European Union V1th Framework (NeuroNE)
  6. Alzheimer's Association
  7. The Psychiatry Research Trust
  8. MRC [G0000749, G0501573] Funding Source: UKRI
  9. Medical Research Council [G0000749, G0501573] Funding Source: researchfish

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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. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

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