title: Inhibition of cyclooxygenase-2 protects motor neurons in an organotypic model of amyotrophic lateral sclerosis.
abstract: 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.
authors.affiliation: Department of Neurology, The Johns Hopkins School of Medicine, Baltimore, MD 21287-7519, USA.
authors.forename: D B
authors.initials: DB
authors.lastname: Drachman
authors.forename: J D
authors.initials: JD
authors.lastname: Rothstein
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000818:Animals; D051546:Cyclooxygenase 2; D004195:Disease Models, Animal; D007527:Isoenzymes / Q000378:metabolism*; D009046:Motor Neurons / Q000378:metabolism*; D009924:Organ Culture Techniques; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011720:Pyrazoles / Q000378:metabolism; D051381:Rats; D013116:Spinal Cord / Q000378:metabolism; D013449:Sulfonamides / Q000378:metabolism; D000096926:Benzenesulfonamides
chemical_list: D051546:Cyclooxygenase 2; D007527:Isoenzymes; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D013449:Sulfonamides; C119130:4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide; D000096926:Benzenesulfonamides