PROGRAMMED CELL DEATH IN THE NERVOUS SYSTEM

我们已经研究了神经系统中的程序性细胞死亡和一般的细胞凋亡的生化机制。(1)为了分析神经系统中的细胞凋亡，我们发展了一种在显微镜下识别凋亡细胞的新方法。这一新的方法使我们能够确定细胞凋亡是发育过程中和MPP+处理后小脑颗粒细胞死亡的方式。(2)制备抗细胞凋亡调控蛋白Bcl2、Bclx和Bax的单抗，探讨其体内外作用机制。抗体显示，在细胞凋亡过程中，Bax从胞浆迁移到细胞膜。(4)利用绿色荧光蛋白标记和跟踪Bax、Bcl一2和Bclxl在细胞凋亡过程中的运动，探讨Bax、Bcl一2和Bclxl在神经元中的运动。我们发现Bax和Bclxl从胞浆转移到有丝分裂原是其细胞凋亡控制机制中的一个重要步骤。(5)发现核糖核酸酶L介导病毒和干扰素诱导的细胞凋亡。(6)我们开发了一种新的方法，通过将Bcl一x转移到细胞表面来阻断细胞的凋亡。程序性细胞死亡；神经系统；细胞凋亡；Bcl-2

We have studied programmed cell death in the nervous system and the biochemical mechanism of apoptosis in general. (1) To analyze apoptosis in the nervous system we developed a new method to identify apoptotic cells under the microscope. This new method allowed us to identify apoptosis as the method of cerebellar granule cell death during development and after MPP+ treatment. (2) We have developed monoclonal antibodies against apoptosis regulatory proteins Bcl-2, Bcl-x, and Bax to probe their mechanism of action in vitro and in vivo. The antibodies reveal that Bax migrates from the cytosol to cell membranes during apoposis. (4) To explore Bax, Bcl-2 and Bcl-xl movement in neurons the green flourescent protein has been used to tag and follow the proteins during apoptosis. We discovered that Bax and Bcl-xl move from the cytosol to the mitochendria as an essential step in their mechanism of apoptosis control. (5) We found RNase L to mediate virus and interferon-induced apoptosis. (6) We developed a new way to block cell apoptosis by delivery of Bcl-x to the cell surface. - programmed cell death; nervous system; apoptosis; Bcl-2