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 language | English |
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Pages (from-to) | 980-983 |
Number of pages | 4 |
Journal | Annals of Neurology |
Volume | 59 |
Issue number | 6 |
Early online date | 17 Apr 2006 |
DOIs | |
Publication status | Published - 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