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

Gabriele Almer, Hitoshi Kikuchi, Peter Teismann, Serge Przedborski

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)980-983
Number of pages4
JournalAnnals of Neurology
Volume59
Issue number6
Early online date17 Apr 2006
DOIs
Publication statusPublished - 1 Jun 2006

Fingerprint

Amyotrophic Lateral Sclerosis
Prostaglandins E
Cyclooxygenase 2
Cyclooxygenase 1
Mutation
Genetic Engineering
Transgenic Mice
Spinal Cord
Superoxide Dismutase-1

Keywords

  • Amyotrophic Lateral Sclerosis
  • Animals
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Dinoprostone
  • Disease Models, Animal
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Nerve Degeneration
  • Spinal Cord
  • Survival

Cite this

Is prostaglandin E(2) a pathogenic factor in amyotrophic lateral sclerosis? / Almer, Gabriele; Kikuchi, Hitoshi; Teismann, Peter; Przedborski, Serge.

In: Annals of Neurology, Vol. 59, No. 6, 01.06.2006, p. 980-983.

Research output: Contribution to journalArticle

Almer, G, Kikuchi, H, Teismann, P & Przedborski, S 2006, 'Is prostaglandin E(2) a pathogenic factor in amyotrophic lateral sclerosis?', Annals of Neurology, vol. 59, no. 6, pp. 980-983. https://doi.org/10.1002/ana.20847
Almer, Gabriele ; Kikuchi, Hitoshi ; Teismann, Peter ; Przedborski, Serge. / Is prostaglandin E(2) a pathogenic factor in amyotrophic lateral sclerosis?. In: Annals of Neurology. 2006 ; Vol. 59, No. 6. pp. 980-983.
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abstract = "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.",
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AU - Kikuchi, Hitoshi

AU - Teismann, Peter

AU - Przedborski, Serge

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N2 - 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.

AB - 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.

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KW - Mice, Knockout

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