Przedborski S, Donaldson D, Jakowec M, Kish S J, Guttman M, Rosoklija G, Hays A P
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Ann Neurol. 1996 Feb;39(2):158-65. doi: 10.1002/ana.410390204.
Amyotrophic lateral sclerosis is a fatal paralytic disorder of unknown cause. Recent evidence implicated the role of free radicals in the death of motor neurons in this disease. To investigate this hypothesis further, we measured the activity of the main free radical scavenging enzymes copper/zinc superoxide dismutase, manganese superoxide dismutase, catalase, and glutathione peroxidase in postmortem brain samples from 9 patients with sporadic amyotrophic lateral sclerosis and from 9 control subjects. We examined samples from the precentral gyrus of the cerebral cortex, a region affected in amyotrophic lateral sclerosis, and from the cerebellar cortex, a region not affected. The two groups did not differ in age or postmortem delay. In the precentral gyrus from amyotrophic lateral sclerosis samples, glutathione peroxidase activity as measured by spectrophotometric assay (13.8 +/- 2.6 nmol/min/mg protein [mean +/- standard error of mean]) was reduced significantly compared to the activity in the precentral gyrus from control samples (22.7 +/- 0.5 nmol/min/mg protein). In contrast, glutathione peroxidase activity was not significantly altered in the cerebellar cortex from amyotrophic lateral sclerosis patients compared to controls. Copper/zinc superoxide dismutase, manganese superoxide dismutase (corrected or not corrected for citrate synthase), and catalase were not significantly altered in the precentral gyrus or cerebellar cortex in the patient samples. This study indicated that glutathione peroxidase activity is reduced in a brain region affected in amyotrophic lateral sclerosis, thus suggesting that free radicals may be implicated in the pathogenesis of the disease.
肌萎缩侧索硬化症是一种病因不明的致命性麻痹疾病。最近有证据表明自由基在该疾病运动神经元死亡中起作用。为进一步研究这一假说，我们测量了9例散发性肌萎缩侧索硬化症患者和9例对照者死后脑样本中主要自由基清除酶铜/锌超氧化物歧化酶、锰超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的活性。我们检查了来自大脑皮质中央前回（肌萎缩侧索硬化症受累区域）和小脑皮质（未受累区域）的样本。两组在年龄或死后延迟方面无差异。在肌萎缩侧索硬化症样本的中央前回中，通过分光光度法测定的谷胱甘肽过氧化物酶活性（13.8±2.6 nmol/分钟/毫克蛋白质[平均值±平均标准误]）与对照样本中央前回中的活性（22.7±0.5 nmol/分钟/毫克蛋白质）相比显著降低。相比之下，与对照组相比，肌萎缩侧索硬化症患者小脑皮质中的谷胱甘肽过氧化物酶活性没有显著改变。患者样本中央前回或小脑皮质中的铜/锌超氧化物歧化酶、锰超氧化物歧化酶（校正或未校正柠檬酸合酶）和过氧化氢酶没有显著改变。这项研究表明，在肌萎缩侧索硬化症受累的脑区域中谷胱甘肽过氧化物酶活性降低，因此提示自由基可能与该疾病的发病机制有关。
