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

Annals of Neurology
Gabriele AlmerSerge Przedborski

Abstract

To elucidate the role of cyclooxygenase-1 (Cox1) and prostaglandin E(2) in ALS neurodegeneration. 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. 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. 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.

References

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Sep 27, 2003·The European Journal of Neuroscience·Christian MaihöfnerDieter Heuss
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Citations

Jun 15, 2011·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Samir S AyoubChristopher Bolton
Mar 29, 2008·Antioxidants & Redox Signaling·Mauro CozzolinoMaria Teresa Carrì
Jul 11, 2012·Mediators of Inflammation·Isabel Vieira de Assis LimaAntonio Carlos Pinheiro de Oliveira
Jul 7, 2018·Muscle & Nerve·Marlena Wosiski-KuhnCarol Milligan
Sep 8, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nadia D'AmbrosiCinzia Volonté

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