Role of Fucosyl Saccharides in Neuronal Communication

描述(申请人提供)：这个项目试图了解岩藻糖糖影响大脑神经细胞之间的识别和交流的分子机制。一些证据表明，岩藻糖α(1-2)半乳糖(Fucα(1-2)Gal)糖在调节神经元连接方面发挥着重要作用，对长期记忆至关重要。然而，人们对它们在大脑中的确切结构或功能知之甚少。这项拟议的研究将化学和神经生物学结合起来，以确定分子成分--即岩藻糖糖、糖蛋白和凝集素--并研究它们调节突触间信息流的机制。这个项目的具体目标是：1.鉴定大脑中的Fucα(1-2)Gal凝集素2.鉴定大脑中的Fucα(1-2)GalGal糖蛋白3.通过检测已识别的凝集素和糖蛋白之间的成对相互作用，以及通过研究它们对神经元形态和突触传递的贡献，来研究Fuc Alpha(1-2)Gal是否具有“识别元件”的功能4.研究Fuc Alpha(1-2)Gal表位是否作为“靶向元件”调节糖蛋白向突触的运输本计划的长期目标是更好地了解神经细胞通讯的分子和细胞基础，最终，是长期记忆的形成。由于该计划采用了一种明显的化学方法，这些研究最终可能会揭示治疗干预的新观点，并使能够调节认知并改善与年龄和神经退行性疾病相关的缺陷的分子的设计成为可能。

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.