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首页> 外文期刊>Archives of neurology. >Mitochondrial respiratory chain dysfunction in muscle from patients with amyotrophic lateral sclerosis.
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Mitochondrial respiratory chain dysfunction in muscle from patients with amyotrophic lateral sclerosis.

机译：线粒体呼吸链的功能障碍肌肉的肌萎缩性脊髓侧索患者硬化。

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BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a major cause of neurological disability and its pathogenesis remains elusive despite a multitude of studies. Although defects of the mitochondrial respiratory chain have been described in several ALS patients, their pathogenic significance is unclear. OBJECTIVE: To review systematically the muscle biopsy specimens from patients with typical sporadic ALS to search for possible mitochondrial oxidative impairment. DESIGN: Retrospective histochemical, biochemical, and molecular studies of muscle specimens. SETTING: Tertiary care university. Subjects Fifty patients with typical sporadic ALS (mean age, 55 years). Main Outcome Measure Number of patients showing a clear muscle mitochondrial dysfunction assessed through histochemical and biochemical muscle analysis. RESULTS: Histochemical data showed cytochrome c oxidase (COX)-negative fibers in 46% patients. Based on COX histochemical activity, patients fell into 4 groups: 27 had normal COX activity; and 8 had mild (2-4 COX-negative fibers of 100 fibers), 8 had moderate (5-10 COX-negative fibers of 100), and 7 had severe (>10 COX-negative fibers of 100) COX deficiency. Spectrophotometric measurement of respiratory chain activities showed that 3 patients with severe histochemical COX deficiency also showed combined enzyme defects. In 1 patient, COX deficiency worsened in a second biopsy taken 9 months after the first. Among the patients with severe COX deficiency, one had a new mutation in the SOD1 gene, another a mutation in the TARDBP gene, and a third patient with biochemically confirmed COX deficiency had multiple mitochondrial DNA deletions detectable by Southern blot analysis. CONCLUSIONS: Our data confirm that the histochemical finding of COX-negative fibers is common in skeletal muscle from patients with sporadic ALS. We did not find a correlation between severity of the oxidative defect and age of the patients or duration of the disease. However, the only patient who underwent a second muscle biopsy did show a correlation between severity of symptoms and worsening of the respiratory chain defect. In 7 patients, the oxidative defect was severe enough to support the hypothesis that mitochondrial dysfunction must play a role in the pathogenesis of the disease.
机译：背景:肌萎缩性脊髓侧索硬化症(ALS)神经系统残疾及其主要原因发病机理仍然是难以捉摸的,尽管许多的研究。呼吸链中描述的几个ALS患者,其致病意义不清楚。肌肉活检患者标本典型的零星的ALS搜索成为可能线粒体氧化损伤。回顾组织化学、生化和分子的研究肌肉标本。三级护理大学。与典型的零星的肌萎缩性侧索硬化症(平均年龄55岁)。主要结果测量显示的患者数量清晰的肌肉线粒体功能障碍评估通过组织化学和生化肌肉分析。细胞色素c氧化酶(COX) -纤维在46%病人。患者分为4组:27考克斯正常活动;100纤维),8温和(5 - 10 COX-negative100)的纤维,7有严重(> 10COX-negative纤维缺考克斯,100)。呼吸的光度测量链活动表明,3例严重的缺组织化学考克斯还显示结合酶缺陷。缺乏恶化在第二个活检9个月后。严重缺考克斯,一个新的突变SOD1基因,另一个在TARDBP突变对生化反应基因,而第三个耐心确认缺考克斯有多个线粒体DNA缺失检测印迹分析。确认的组织化学的发现COX-negative纤维在骨骼肌中很常见从零星的ALS患者。氧化的严重程度之间的相关性缺陷和年龄的病人或持续时间疾病。第二个肌肉活检显示相关之间的严重程度和恶化的症状呼吸链缺陷。氧化缺陷严重程度足以支持假设线粒体功能障碍在疾病的发病机制中发挥作用。

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