Inhibition of cyclooxygenase-2 protects motor neurons in an organotypic model of amyotrophic lateral sclerosis

Ann Neurol. 2000 Nov;48(5):792-5.


The pathogenesis of motor neuron loss in amyotrophic lateral sclerosis (ALS) is thought to involve both glutamate-mediated excitotoxicity and oxidative damage due to the accumulation of free radicals and other toxic molecules. Cyclooxygenase-2 (COX-2) may play a key role in these processes by producing prostaglandins, which trigger astrocytic glutamate release, and by inducing free radical formation. We tested the effects of COX-2 inhibition in an organotypic spinal cord culture model of ALS. The COX-2 inhibitor (SC236) provided significant protection against loss of spinal motor neurons in this system, suggesting that it may be useful in the treatment of ALS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / metabolism*
  • Animals
  • Cyclooxygenase 2
  • Disease Models, Animal
  • Isoenzymes / metabolism*
  • Motor Neurons / metabolism*
  • Organ Culture Techniques
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Pyrazoles / metabolism
  • Rats
  • Spinal Cord / metabolism
  • Sulfonamides / metabolism


  • 4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide
  • Isoenzymes
  • Pyrazoles
  • Sulfonamides
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases