SPHINGOGLYCOLIPIDS IN NORMAL AND PATHOLOGICAL BRAINS

该项目的主要目标是研究分布， 鞘糖脂（GSL）的结构、代谢和功能， 特别是神经节苷脂在正常和病理组织、细胞和 CNS的亚细胞器。 我们将进行隔离， 新GSL的表征和新生物合成的阐明 途径。 我们将开发新的方法来调查他们的 亚细胞定位和周转，以及它们的化学合成。 我们还将制定新的战略， 二级结构，并将这些信息与其功能作用联系起来 in biological生物membrane膜. 髓磷脂和 少突胶质细胞将通过代谢的成分， 是大脑发育过程中这两个部分所固有的。 特别 重点将放在髓鞘脂蛋白的功能作用 髓鞘形成和髓鞘膜维持中的相互作用 完整 髓鞘脂质-蛋白质相互作用的模式将是 通过核磁共振等物理技术进行研究 光谱法和差示扫描量热法。 这种知识是 对于理解髓磷脂相关神经元的生理作用至关重要。 神经氨酸酶与髓鞘碱性蛋白水解调节 髓鞘形成和脱髓鞘。 最后，我们将调查 通过研究慢病毒因子的组成和 羊瘙痒症小鼠脑中膜神经节苷脂的代谢。 我们还计划 研究神经节苷脂在各种神经系统中的表达， 疾病和表现出星形细胞增多症的动物模型中， 更好地了解异常神经节苷脂代谢之间的关系 和生理功能障碍。

The major objectives of this project are to study the distribution, structure, metabolism, and function of glycosphingolipids (GSLs), particularly gangliosides, in normal and pathological tissues, cells and subcellular organelles of the CNS. We will engage in the isolation and characterization of new GSLs and in the elucidation of new biosynthetic pathways. We will develop new methodologies for investigating their subcellular localization and turnover, and for their chemical synthesis. We will also develop new strategies for elucidating their primary and secondary structures and relate this information to their functional role in biological membranes. The relationship between myelin and oligodendroglia will be examined through the metabolism of components that are intrinsic to these two compartments during brain development. Special emphasis will be placed on the functional role of myelin lipid-protein interactions in myelination and the maintenance of myelin membrane integrity. The mode of myelin lipid-protein interaction will be investigated by such physical techniques as nuclear magnetic resonance spectrometry and differential scanning calorimetry. This knowledge is essential in understanding the physiological role of myelin-associated neuraminidase and the regulation of proteolysis of myelin basic protein myelination and demyelination. Finally, we will investigate the pathogenesis of slow virus agents by studying the composition and metabolism of membrane ganglioside in scrapie mouse brains. We also plan to investigate the expression of gangliosides in a variety of neurological diseases and in an animal model which exhibit astrocytosis in order to better understand the relationship between abnormal ganglioside metabolism and physiological dysfunction in these neurological disorders.