Drachman D B, Rothstein J D
Department of Neurology, The Johns Hopkins School of Medicine, Baltimore, MD 21287-7519, USA.
Ann Neurol. 2000 Nov;48(5):792-5.
The pathogenesis of motor neuron loss in amyotrophic lateral sclerosis (ALS) is thought to involve both glutamate-mediated excitotoxicity and oxidative damage due to the accumulation of free radicals and other toxic molecules. Cyclooxygenase-2 (COX-2) may play a key role in these processes by producing prostaglandins, which trigger astrocytic glutamate release, and by inducing free radical formation. We tested the effects of COX-2 inhibition in an organotypic spinal cord culture model of ALS. The COX-2 inhibitor (SC236) provided significant protection against loss of spinal motor neurons in this system, suggesting that it may be useful in the treatment of ALS.
肌萎缩侧索硬化症（ALS）中运动神经元丧失的发病机制被认为涉及谷氨酸介导的兴奋性毒性以及由于自由基和其他有毒分子积累所导致的氧化损伤。环氧合酶-2（COX-2）可能通过产生前列腺素（引发星形胶质细胞释放谷氨酸）以及诱导自由基形成，在这些过程中发挥关键作用。我们在ALS的器官型脊髓培养模型中测试了COX-2抑制的效果。COX-2抑制剂（SC236）在该系统中为脊髓运动神经元的丧失提供了显著保护，这表明它可能对ALS的治疗有用。
