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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Is prostaglandin E(2) a pathogenic factor in amyotrophic lateral sclerosis?

OBJECTIVE: To elucidate the role of cyclooxygenase-1 ( Cox1) and prostaglandin E(2) in ALS neurodegeneration. METHODS: Mutation in superoxide dismutase-1 is a cause of the fatal paralytic disorder amyotrophic lateral sclerosis. Inhibition of cyclooxygenase-2 (Cox-2) in transgenic mice expressing an amyotrophic lateral sclerosis-linked superoxide dismutase-1 mutation led to the idea that prostaglandin E(2), the main synthetic product of Cox-2, is pathogenic in amyotrophic lateral sclerosis. RESULTS: Herein, we show by genetic intervention that prostaglandin E(2) in the spinal cord is mainly produced by Cox-1, and that ablation of Cox-1 fails to attenuate neurodegeneration. INTERPRETATION: The previously documented role of Cox-2 in ALS neurodegeneration in this particular mouse model occurs through a mechanism independent of prostaglandin E(2). Furthermore, plans to use selective Cox-1 inhibitors for neuroprotection in ALS are unlikely to be fruitful.[1]


  1. Is prostaglandin E(2) a pathogenic factor in amyotrophic lateral sclerosis? Almer, G., Kikuchi, H., Teismann, P., Przedborski, S. Ann. Neurol. (2006) [Pubmed]
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