Role of Fucosyl Saccharides in Neuronal Communication

岩藻糖基糖在神经元通讯中的作用

• 批准号: 6747556
• 负责人: Linda C Hsieh-Wilson
• 金额: $ 40.61万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-15 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6747556
• 关键词: SDS polyacrylamide gel electrophoresis; affinity chromatography; brain; carbohydrate structure; confocal scanning microscopy; fluorescence microscopy; fucose; galactose; glycoproteins; immunoprecipitation; intermolecular interaction; intracellular transport; laboratory rat; lectin; long term memory; mass spectrometry; matrix assisted laser desorption ionization; molecular shape; neural information processing; neural transmission; neurons; protein transport; surface plasmon resonance; synaptogenesis

DESCRIPTION (provided by applicant): This project seeks to understand the molecular mechanisms by which fucosyl saccharides influence recognition and communication between nerve cells in the brain. Several lines of evidence suggest that fucose alpha (1-2) galactose (Fuc alpha(1-2)Gal) saccharides play an important role in modulating neuronal connections important for long-term memory. Relatively little is known, however, about their precise structures or function in the brain. The proposed research combines chemistry and neurobiology to identify the molecular components - i.e., fucosyl saccharides, glycoproteins and lectins - and to study the mechanisms by which they regulate the flow of information across the synapse. The specific aims of this project are to: 1. Identify Fuc alpha(1-2)Gal lectins in the brain 2. Identify Fuc alpha(1-2)Gal glycoproteins in the brain 3. Investigate whether the Fuc alpha(1-2)Gal functions as a "recognition element" by examining pair wise interactions between identified lectins and glycoproteins and by studying their contribution to neuronal morphology and synaptic transmission 4. Investigate whether the Fuc alpha(1-2)Gal epitope functions as a "targeting element" to regulate the trafficking of glycoproteins to the synapse The long-term goal of this program is to provide a better understanding of the molecular and cellular basis of nerve cell communications and, ultimately, long-term memory formation. Because the program takes a distinctly chemical approach, these studies may ultimately reveal novel points of therapeutic intervention and enable the design of molecules capable of modulating cognition and improving deficits associated with age and neurodegenerative disease.

项目描述（申请人提供）：本项目旨在了解岩藻糖基糖苷影响大脑神经细胞之间识别和通信的分子机制。几条证据表明，岩藻糖α（1-2）半乳糖（Fuc α（1-2）Gal）β在调节对长期记忆重要的神经元连接中发挥重要作用。然而，人们对它们在大脑中的精确结构或功能知之甚少。这项拟议中的研究结合了化学和神经生物学来识别分子成分，岩藻糖基糖苷，糖蛋白和凝集素-并研究它们调节突触信息流的机制。该项目的具体目标是：1.鉴定脑中的Fuc α（1-2）半乳糖凝集素2.鉴定脑中的Fuc α（1-2）Gal糖蛋白3.研究是否Fuc alpha（1-2）Gal功能作为一个“识别元件”，通过检查成对的相互作用之间的鉴定凝集素和糖蛋白，并通过研究它们的贡献，神经元形态和突触传递4。研究Fuc alpha（1-2）Gal表位是否作为“靶向元件”发挥作用，以调节糖蛋白向突触的运输。该计划的长期目标是更好地理解神经细胞通信的分子和细胞基础，并最终形成长期记忆。由于该计划采用了独特的化学方法，这些研究最终可能揭示治疗干预的新点，并能够设计能够调节认知和改善与年龄和神经退行性疾病相关的缺陷的分子。