PROGRAMMED CELL DEATH IN THE NERVOUS SYSTEM

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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