CHANGES IN GENE-TRANSCRIPTION DURING A BETA-MEDIATED CELL-DEATH

The a beta peptide induces cell death in neurons grown in cell culture , Previous studies have shown that the mechanism of a beta-mediated ce ll death of central nervous system neurons appears to be via apoptosis , Apoptosis is an active process that involves both gene transcription and translation, Using semi-quantitative polymerase chain reaction, w e have analyzed the levels of a variety of transcripts in primary neur onal cultures treated with a beta that are likely to play important ro les in apoptosis, Following addition of 10 mu M a beta(1-42) the immed iate early response gene, c-fos, shows a rapid and sustained increase in transcript level while c-jun levels increase at a slower rate, Bcl- 2 and its homologues, bcl-X and bar, also increase in amount with bcl- 2 and bcl-X increasing more rapidly than bar. These data provide suppo rt indicating that a beta-mediated cell death in central nervous syste m neurons is an active process similar to that seen in apoptosis.