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α(1，2)半乳糖(Fucα(1，2)Gal)糖影响大脑神经细胞之间识别和交流的分子机制。一些证据表明，Fuccx(1，2)半乳糖在调节神经细胞之间的连接方面发挥着重要作用，这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。这项拟议的研究结合了化学和神经生物学，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。 本项目的具体目标是：1.设计和合成化学探针以研究岩藻糖-半乳糖在大脑中的作用2.应用化学探针结合先进的质谱学方法，鉴定(A)岩藻糖-半乳糖结合蛋白(即凝集素)和(B)岩藻糖-半乳糖糖蛋白3.利用免疫共沉淀和荧光显微镜研究凝集素与前一节中确定的糖蛋白之间的成对相互作用4.研究岩藻糖-半乳糖糖在神经细胞形态和功能调节中的作用 这个项目的长期目标是更好地理解学习和记忆的分子和细胞基础。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 fucose alpha (1,2) galactose (Fuc alpha (1,2)Gal) saccharides influence recognition and communication between nerve cells in the brain. Several lines of evidence suggest that Fuccx (1,2) Gal saccharides play an important role in modulating the connections between nerve cells important for long-term memory. However, relatively little is known about their precise structure 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. Design and synthesize chemical probes to study the role of fucose-galactose in the brain 2. Apply the chemical probes, in conjunction with advance mass spectrometry methods, to identify (a) fucose-galactose binding proteins (i.e. lectins) and (b) fucose-galactose glycoproteins 3. Use co-immunoprecipitation and fluorescence microscopy studies to investigate pairwise interactions between the lectins and glycoproteins identified in the previous section 4. Study the role of fucose-galactose saccharides in regulating the morphology and function of nerve cells The long-term goal of this program is to provide a better understanding of the molecular and cellular underpinnings of learning and memory. 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.