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

Keywords

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

Fingerprint Dive into the research topics of 'Is prostaglandin E(2) a pathogenic factor in amyotrophic lateral sclerosis?'. Together they form a unique fingerprint.

  • Cite this