Almer Gabriele, Kikuchi Hitoshi, Teismann Peter, Przedborski Serge
Department of Neurology, Columbia University, New York, NY 10032, USA.
Ann Neurol. 2006 Jun;59(6):980-3. doi: 10.1002/ana.20847.
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.
阐明环氧化酶-1（Cox1）和前列腺素E2在肌萎缩侧索硬化症神经退行性变中的作用。
超氧化物歧化酶-1突变是致命性麻痹性疾病肌萎缩侧索硬化症的病因之一。在表达与肌萎缩侧索硬化症相关的超氧化物歧化酶-1突变的转基因小鼠中抑制环氧化酶-2（Cox-2），这引发了一种观点，即Cox-2的主要合成产物前列腺素E2在肌萎缩侧索硬化症中具有致病性。
在此，我们通过基因干预表明，脊髓中的前列腺素E2主要由Cox-1产生，并且Cox-1的缺失并不能减轻神经退行性变。
在这个特定小鼠模型中，先前记录的Cox-2在肌萎缩侧索硬化症神经退行性变中的作用是通过一种独立于前列腺素E2的机制发生的。此外，计划使用选择性Cox-1抑制剂对肌萎缩侧索硬化症进行神经保护不太可能取得成效。
