OXIDATIVE METABOLISM IN INHERITED NEUROLOGICAL DISEASES AND IN MOLLICUTES

遗传性神经疾病和软体中的氧化代谢

• 批准号: 3922561
• 负责人: G CONSTANTOPOULOS
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3922561
• 关键词: Friedreich's ataxia; Mycoplasmatales; bacterial disease; electron microscopy; fibroblasts; genetic disorder; glutamate dehydrogenase; human tissue; inborn metabolism disorder; malate dehydrogenase; mitochondria; nervous system disorder; nervous system disorder diagnosis; oxidation; pyruvate dehydrogenase

In increasing amount of evidence points to a possible defect in oxidative metabolism in patients with certain inherited neurological disorders. Thus, a defect in the pyruvate oxidation system has been shown in some patients with lactic acidemia and diffuse neurologic disease, of the mitochondrial malic enzyme in patients with Friedreich's ataxia, and a partial deficiency of glutamate dehydrogenase in some patients with olivopontocerebellar degeneration. However, there is much controversy about the exact enzymatic defect(s). The objective of this project is the elucidation of the defect in some of these patients or in skin fibroblasts derived from such patients. For this purpose we are assaying a number of mitochondrial and non-mitochondrial enzymes in fibroblasts or leukocytes and we have initiated electron microscopic studies of the mitochondria. We become interested in the mollicutes because contamination of fibroblast cultures with mollicutes interfered with the assay of pyruvate dehydrogenase complex in these cells. The oxidative metabolism of mollicutes is poorly understood. Hopefully, the elucidation of the defect in these diseases will help in the diagnosis and therapeutic intervention in the patients. Knowledge of the physiology of mollicutes may help in understanding the pathogenicity of these organisms.

越来越多的证据表明， 某些遗传病患者的氧化代谢 神经系统疾病 因此，丙酮酸氧化的缺陷 系统已被证明在一些患者的乳酸血症， 弥漫性神经系统疾病，线粒体苹果酸酶， Friedreich共济失调患者，以及部分缺乏 橄榄体脑桥小脑型谷氨酸脱氢酶 退化 然而，关于确切的 酶缺陷。 该项目的目标是 阐明这些患者或皮肤中的缺陷 成纤维细胞来源于这些患者。 为此，我们 分析大量线粒体和非线粒体酶 在成纤维细胞或白细胞中， 线粒体的显微镜研究。 我们开始对 因为成纤维细胞培养物被 柔膜菌干扰丙酮酸脱氢酶测定 在这些细胞中。 柔膜菌的氧化代谢是 不太了解。 希望，对缺陷的解释 这些疾病将有助于诊断和治疗 对患者的干预。 生理学知识 柔膜菌可能有助于了解这些病原体的致病性， 有机体