S-100B--NEURONAL GLIAL LINK TO ALZHEIMERS DISEASE

该计划项目包括建立的凝聚力的努力， 来自不同机构的科学家。 核心和项目是 综合测试的假设，S-100 β是连接到 与阿尔茨海默病（AD）相关的神经病理学，以及 进一步了解神经元/神经胶质细胞的相互作用， CNS生长因子的操作。 一个行政核心，五个研究 核心的建议，以促进必要的相互作用，以成本- 有效地利用个人的专业知识和良好的支持 在各自的研究中心提供设施。 五个研究 这些项目将涉及利用组织培养的三个总体研究领域。 研究领域1将研究影响因素的详细作用， 星形胶质细胞调节S-100 β的合成和释放（例如，IL-1，5- HT、Ca++和糖皮质激素）。 该研究领域的成果将 提供了关键的星形胶质细胞调节物质的身份线索， 可能在AD中发生改变，并且可以在我们广泛的收集中进行分析。 老年痴呆症的大脑 研究领域2将研究分子和 暴露于s-100 β导致星形胶质细胞的细胞事件。 信号转导通路和星形胶质细胞形态学的变化， 将研究扩散问题。 研究领域3将探索机制 S-100 β对神经突延伸的作用。 S-100 beta是否进入 神经元与特定微管相关蛋白相互作用和/或 它是否与细胞表面受体结合并通过特异性的 第二信使系统？ 从这三个研究领域获得的结果可以被翻译 用整个动物进行体内实验。 程序，如Cell 移植、原位杂交和免疫细胞化学可以 应用于成年或老年动物的特定脑区。 预测 将在人类死后组织上进行测试， 包括大量的AD大脑 我们的多学科努力 不仅仅是了解星形胶质细胞/神经元 互动，但努力回答S-100 beta的作用的基本问题 老年痴呆症

The Program Project consists of the cohesive efforts of established scientists from separate institutions. The CORES and projects are integrated to test the hypothesis that S-100beta is linked to the neuropathology associated with Alzheimer's Disease (AD), as well as to further our understanding of neuronal/glial interactions in the control and operation of CNS growth factors. An administrative core and five research cores are proposed to facilitate the interactions necessary to cost- effectively utilize the individuals' expertise and the excellent support facilities available at the respective research centers. Five research projects will address three overall research areas using tissue culture. Research Area 1 will be to study the detailed actions of factors acting on astrocytes to regulate the synthesis and release of S-100beta (eg. IL-1, 5- HT, Ca++, and glucocorticoids). The results of this research area will provide clues to the identity of key astrocytic regulatory-substances that may be altered in AD, and which can be analyzed in our extensive collection of Alzheimer's brains. Research Area 2 will examine the molecular and cellular events in astrocytes resulting from exposure to s-100beta. Changes in signal transduction pathways and in astrocytic morphology and proliferation will be studied. Research Area 3 will explore the mechanism of action of S-100beta on neurite extension. Does S-100beta enter the neurons to interact with specific microtubule-associated-proteins and/or does it bind to a cell surface receptor and produce a response via specific second messenger systems? The Results obtained from these three research areas can then be translated into in vivo experiments using whole animals. Procedures such as cell transplantation, in situ hybridization and immunocytochemistry can be applied to specific brain regions in the adult or aged animal. Predictions arising from these studies will be tested on human post mortem tissue which includes a large collection of AD brains. Our multidisciplinary efforts are not concerned solely with understanding astroglial/neuronal interactions but strives to answer basic questions of the role of S-100beta in Alzheimer's disease.