Ferrante R J, Browne S E, Shinobu L A, Bowling A C, Baik M J, MacGarvey U, Kowall N W, Brown R H, Beal M F
Geriatric Research Education Clinical Center, VA Medical Center, Bedford, Massachusetts, U.S.A.
J Neurochem. 1997 Nov;69(5):2064-74. doi: 10.1046/j.1471-4159.1997.69052064.x.
Some cases of autosomal dominant familial amyotrophic lateral sclerosis (FALS) are associated with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1), suggesting that oxidative damage may play a role in ALS pathogenesis. To further investigate the biochemical features of FALS and sporadic ALS (SALS), we examined markers of oxidative damage to protein, lipids, and DNA in motor cortex (Brodmann area 4), parietal cortex (Brodmann area 40), and cerebellum from control subjects, FALS patients with and without known SOD mutations, SALS patients, and disease controls (Pick's disease, progressive supranuclear palsy, diffuse Lewy body disease). Protein carbonyl and nuclear DNA 8-hydroxy-2'-deoxyguanosine (OH8dG) levels were increased in SALS motor cortex but not in FALS patients. Malondialdehyde levels showed no significant changes. Immunohistochemical studies showed increased neuronal staining for hemeoxygenase-1, malondialdehyde-modified protein, and OH8dG in both SALS and FALS spinal cord. These studies therefore provide further evidence that oxidative damage may play a role in the pathogenesis of neuronal degeneration in both SALS and FALS.
一些常染色体显性遗传性家族性肌萎缩侧索硬化症（FALS）病例与编码铜/锌超氧化物歧化酶（SOD1）的基因突变有关，这表明氧化损伤可能在肌萎缩侧索硬化症（ALS）的发病机制中起作用。为了进一步研究FALS和散发性ALS（SALS）的生化特征，我们检测了来自对照受试者、有和没有已知SOD突变的FALS患者、SALS患者以及疾病对照（匹克氏病、进行性核上性麻痹、弥漫性路易体病）的运动皮质（布罗德曼第4区）、顶叶皮质（布罗德曼第40区）和小脑中蛋白质、脂质和DNA氧化损伤的标志物。SALS运动皮质中的蛋白质羰基和核DNA 8-羟基-2'-脱氧鸟苷（OH8dG）水平升高，但FALS患者中未升高。丙二醛水平无显著变化。免疫组织化学研究显示，SALS和FALS脊髓中血红素加氧酶-1、丙二醛修饰蛋白和OH8dG的神经元染色均增加。因此，这些研究提供了进一步的证据，表明氧化损伤可能在SALS和FALS的神经元变性发病机制中起作用。
