COMPLEX GLYCOLIPIDS OF BRAIN AND RELATED SYSTEMS

脑及相关系统的复杂糖脂

• 批准号: 3396830
• 负责人: ABRAHAM ROSENBERG
• 金额: $ 20.09万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-12-01 至 1986-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3396830
• 关键词: Gaucher's disease; Tay Sachs disease; brain metabolism; chromatography; enzyme complex; exo alpha sialidase; glycosphingolipids; human tissue; immunochemistry; inborn metabolism disorder; lipid metabolism; multiple sclerosis; muscular dystrophy; nervous system infection; neurotoxins; radiotracer; tissue /cell culture; virus diseases

To provide information on the metabolism of glycosphingolipids in vivo, using cultured skin fibroblasts from normal donors and donors with the neurological lipid-storage disorders, Gaucher's and Tay-Sachs Diseases with emphasis upon isolation from these cells, purification, and characterization of the deficient hydrolases, regulatory proteins, and activating co-factors, using chromatographic and immunologic techniques. This information should lead to steps aimed at a logical control of these destructive diseases. To investigate the role of beta-galactoside-specific lectin and complex glycosphingolipids in the mechanism of chick embryo myoblast fusion in culture, and the effects of competitive oligosaccharides, lectins, and pathogenic proteins, utilizing techniques for specific labelling of glycosphingolipids in vivo and affinity chromatographic and immunological approach to lectin identification, so as to arrive at an approach toward the correction of the defects in muscular dystrophies and multiple sclerosis. To investigate the role of synaptic sialidase-sialoprotein-sialolipid complexes in neurotransmitter binding and release by specifically labelling, isolating by affinity chromatography, disruption and componential characterization of serotonergic nerve endings from mammalian brain. The findings should aid in an understanding of faulty brain function and the destructive effects of hallucinogens and neurotoxins. To investigate the role of ecto-sialidase of herpes-virus transformed cells in culture, using chromatographic and specific radioactive tracer techniques to trace the effects of this enzyme on the metabolism of cell surface sialic acid and the controlling influence of the latter on ecto-enzymes involved in the breakdown of the neural cell guanyl cyclase activator, acetylcholine. This information should be helpful in approaching a rational therapy for virally induced neuropathies and neuro-oncogenicity.

为了提供体内鞘糖脂代谢的信息，使用 培养的皮肤成纤维细胞来自正常供体和具有神经系统疾病的供体， 高雪氏病和泰-萨克斯病，重点是 从这些细胞中分离、纯化和表征缺陷的 水解酶、调节蛋白和活化辅因子， 色谱和免疫技术。 这些信息应该会导致 这些措施旨在合理控制这些破坏性疾病。 目的探讨β-半乳糖苷特异性凝集素及其复合物在抗肿瘤中的作用。 鞘糖脂在鸡胚成肌细胞融合机制中的作用， 以及竞争性寡糖、凝集素和致病性 蛋白质，利用技术的具体标记的鞘糖脂， 凝集素的体内亲和层析和免疫学方法 识别，以达到对纠正的方法， 肌肉萎缩症和多发性硬化症的缺陷。 探讨突触唾液酸酶-唾液酸蛋白-唾液酸脂复合物的作用 在神经递质的结合和释放中， 亲和层析，破坏和组分表征 哺乳动物脑中的肾上腺素能神经末梢。 这些发现应该有助于 理解大脑功能缺陷和 致幻剂和神经毒素 目的：探讨疱疹病毒转化细胞外唾液酸酶在疱疹病毒感染中的作用。 培养，使用色谱和特定的放射性示踪技术， 追踪这种酶对细胞表面唾液酸代谢的影响 以及后者对参与细胞外酶的控制作用。 神经细胞鸟苷酸环化酶激活剂乙酰胆碱的分解。 这 信息应该有助于接近合理的治疗病毒性 诱发的神经病变和神经致癌性。