Is prostaglandin E2 a pathogenic factor in amyotrophic lateral sclerosis?

✍ Scribed by Gabriele Almer; Hitoshi Kikuchi; Peter Teismann; Serge Przedborski

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 158 KB
• Volume: 59
• Category: Article
• ISSN: 0364-5134
• DOI: 10.1002/ana.20847

✦ Synopsis

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. Ann Neurol 2006