DRUG INTERACTIONS WITH BRAIN MICROTUBULE PROTEINS

药物与脑微管蛋白的相互作用

• 批准号: 3395257
• 负责人: LESLIE WILSON
• 金额: $ 17.29万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-07-01 至 1986-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3395257
• 关键词: brain metabolism; central nervous system; chemical structure function; colchicine; drug adverse effect; drug metabolism; gel electrophoresis; polymerization; scintillation counter; vinblastine

Microtubules are widely distributed in eucaryotic cells and tissues, and are especially abundant in the central nervous system. They are essential to a large number of cellular processes, particularly those concerned with the development and maintenance of cell shape, changes in cell shape, and certain forms of cell motility. It is evident that microtubules must play vital roles in CNS function. For example, they appear to be essential to the development and maintenance of the asymmetric shape characteristic of neuronal cells; and it seems likely that they are involved in both slow and fast axoplasmic transport. However, there is as yet no biochemically defined knowledge as to what the true mechanistic functions of microtubules are, and the specific role(s) of microtubules in the CNS remain largely unknown. The main objectives of this research are to characterize brain microtubule (neurotubule) biochemistry and function with the use of two experimental approaches. One approach focuses on investigation of the biochemical properties of tubulin and other microtubule-associated proteins from the chick and bovine CNS. Some of the specific questions will be concerned with characterization of the subpopulations of microtubules in the CNS, and with regulation of opposite-end assembly and disassembly of brain microtubules. The second approach involves investigation of the biochemical mechanisms of action of drugs that inhibit microtubule polymerization. Studies on the interactions of drugs with tubulin not only yield information on the biochemical mechanisms of action of the drugs, but also provide valuable information on the biochemical properties and functional roles of microtubles. The purpose of these studies is to define the biochemical properties of microtubule protein which are related to microtubule functions, with the long-term goal of understanding the roles of microtubules in relation to brain function.

微管广泛分布于真核细胞和组织中， 尤其是在中枢神经系统中含量丰富。 它们对一个 大量的细胞过程，特别是那些与 细胞形状的发育和维持，细胞形状的变化，以及某些 细胞运动的形式。 很明显，微管必须发挥重要作用， 中枢神经系统功能。 例如，它们似乎对发展 和维持神经元细胞的不对称形状特征;并且 它们似乎参与了慢轴浆运输和快轴浆运输。 然而，目前还没有生物化学定义的知识，以什么是真正的 微管的机械功能是，和特定的作用（S） 中枢神经系统中的微管仍然是未知的。 本研究的主要目的是表征脑微管 （神经管）生物化学和功能与使用两个实验 接近。 一种方法侧重于调查的生化特性 鸡和牛的微管蛋白和其他微管相关蛋白 CNS。 一些具体问题将涉及 中枢神经系统中的微管亚群，以及 脑微管的相反端组装和拆卸。 第二 方法包括研究药物作用的生化机制 抑制微管聚合。 药物相互作用研究 与微管蛋白的相互作用不仅提供了关于生物化学作用机制的信息， 同时也提供了关于药物的生物化学的有价值的信息。 微管的性质和功能作用。这些研究旨在 确定微管蛋白的生化特性，这些特性与 微管功能，长期目标是了解微管的作用， 微管与大脑功能的关系。