PROGRAMMED CELL DEATH IN THE NERVOUS SYSTEM

神经系统中的程序性细胞死亡

• 批准号: 6111900
• 负责人: RICHARD J. YOULE
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6111900
• 关键词: T lymphocyte; apoptosis; cell growth regulation; cytotoxicity; developmental immunology; developmental neurobiology; heterokaryon; human subject; human tissue; methylphenyltetrahydropyridine; monoclonal antibody; neuroprotectants; neurotoxins; tissue /cell culture

We have studied programmed cell death in the nervous system and the biochemical mechanism of apoptosis in general. To approach the nervous system, more sensitive and in situ methods are needed to identify cells undergoing programmed cell death. We have developed new methods to identify apoptotic cells under the microscope. This new method allowed us to identify apoptosis as the method of cerebellar granule cell death after MPP+ treatment in vitro. (1) We have also developed a molecular detection method to measure DNA strand breaks in situ. This allows us to examine brains of animals undergoing neurodegenerative changes during ischemia, MPTP treatment, and during development. This new method has allowed us to determine the role apoptosis plays during development and during various disease states of the nervous system. (2) We have developed monoclonal antibodies against apoptosis regulatory genes Bcl-2, Bcl-x, and Bax to probe the regulation of apoptosis in vitro and in vivo. The antibodies reveal that Bax migrates from the cytosol to mitochondrial membranes during apoposis. To explore Bax, Bcl-2 and Bcl-xl trafficking in neurons the green flourescent protein has been used to tag and follow the proteins during apoptosis. (3) We discovered that Bax and Bcl-xl move from the cytosol to the mitochendria as an essential step in their mechanism of apoptosis control. (4) We found RNaseL to modiate virus and interferon induced apoptosis.

我们已经研究了细胞的程序性死亡， 神经系统和细胞凋亡的生化机制 将军为了接近神经系统，更敏感和原位 需要方法来识别经历编程细胞的细胞， 死亡我们已经开发了新的方法来识别凋亡细胞 在显微镜下。这种新方法使我们能够识别 凋亡作为MPP+后小脑颗粒细胞死亡的方法 体外治疗(1)我们还开发了一种分子 原位测量DNA链断裂的检测方法。这 让我们能够检查动物的大脑 缺血、MPTP治疗期间的神经退行性变化，以及 在发展过程中。这种新方法使我们能够确定 细胞凋亡在发育过程中和各种 神经系统的疾病状态。(2)我们已经开发 抗细胞凋亡调节基因Bcl-2的单克隆抗体， Bcl-x和Bax在体外和体内研究细胞凋亡的调节 vivo.抗体显示Bax从细胞质迁移到 线粒体膜凋亡的过程。探讨Bax、Bcl-2 和Bcl-xl在神经元中的运输，绿色荧光蛋白具有 用于标记和跟踪凋亡过程中的蛋白质。(3)我们 发现Bax和Bcl-xl从细胞质移动到细胞质， 线粒体作为其凋亡机制中的重要步骤 控制(4)我们发现RNaseL修饰病毒和干扰素 诱导凋亡。