Cyclooxygenase 2 inhibition protects motor neurons and prolongs survival in a transgenic mouse model of ALS
Autor: | Gabrielle Almer, Krystl Frank, Serge Przedborski, Margaret Dykes-Hoberg, Jeffrey D. Rothstein, Peter Teismann, Daniel B. Drachman |
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Rok vydání: | 2002 |
Předmět: |
Male
Excitotoxicity Mice Transgenic Pharmacology medicine.disease_cause Dinoprostone Proinflammatory cytokine Mice medicine Animals Humans Cyclooxygenase Inhibitors Prostaglandin E2 Amyotrophic lateral sclerosis Motor Neurons Sulfonamides biology Cyclooxygenase 2 Inhibitors Amyotrophic Lateral Sclerosis Glutamate receptor Membrane Proteins Motor neuron medicine.disease Astrogliosis Isoenzymes Survival Rate Disease Models Animal medicine.anatomical_structure Neurology Celecoxib Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Immunology biology.protein Pyrazoles Female Neurology (clinical) Cyclooxygenase medicine.drug |
Zdroj: | Annals of neurology. 52(6) |
ISSN: | 0364-5134 |
Popis: | The pathogenesis of cell death in amyotrophic lateral sclerosis (ALS) may involve glutamate-mediated excitotoxicity, oxidative damage, and apoptosis. We used a transgenic mouse model of ALS to determine the effect of inhibition of cyclooxygenase-2 in treating the disease. Cyclooxygenase-2, present in spinal neurons and astrocytes, catalyzes the synthesis of prostaglandin E2. Prostaglandin E2 stimulates glutamate release from astrocytes, whereas cyclooxygenase-2 also plays a key role in the production of proinflammatory cytokines, reactive oxygen species, and free radicals. Treatment with a selective cyclooxygenase-2 inhibitor, celecoxib, markedly inhibited production of prostaglandin E2 in the spinal cords of ALS mice. Celecoxib treatment significantly delayed the onset of weakness and weight loss and prolonged survival by 25%. Spinal cords of treated ALS mice showed significant preservation of spinal neurons and diminished astrogliosis and microglial activation. Our results suggest that cyclooxygenase-2 inhibition may benefit ALS patients. |
Databáze: | OpenAIRE |
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