Role of Fucosyl Saccharides in Neuronal Communication

描述（由申请人提供）：本项目旨在了解聚焦糖影响大脑神经细胞之间识别和通讯的分子机制。多项证据表明，聚焦α(1-2)半乳糖（Fuc α (1-2)Gal）糖在调节长期记忆中重要的神经元连接中起着重要作用。然而，人们对它们在大脑中的精确结构或功能知之甚少。这项拟议中的研究将化学和神经生物学结合起来，以确定分子成分——即焦糖、糖蛋白和凝集素——并研究它们调节突触间信息流动的机制。该项目的具体目标是：1。鉴定脑内Fuc α (1-2)Gal凝集素脑内Fuc α (1-2)Gal糖蛋白的鉴定通过检查已鉴定的凝集素和糖蛋白之间的成对相互作用，以及研究它们对神经元形态和突触传递的贡献，研究Fuc α (1-2)Gal是否作为“识别元件”起作用4。研究Fuc α (1-2)Gal表位是否作为一种“靶向元件”来调节糖蛋白向突触的运输。该项目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。由于该项目采用了一种独特的化学方法，这些研究可能最终揭示治疗干预的新观点，并使分子能够调节认知，改善与年龄和神经退行性疾病相关的缺陷。

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.