MODULATION OF THE PC12 CELL RESPONSE TO NERVE GROWTH-FACTOR BY ANTISENSE OLIGONUCLEOTIDE TO AMYLOID PRECURSOR PROTEIN

1. The amyloid precursor protein (APP) is widely distributed among euk aryotic cells, however, its precise role in cellular functioning is no t fully clarified, APP is glycoprotein membrane constituent and it may facilitate membrane associated functions. 2. The aim of the present s tudy was to examine the possibility that APP may play a role in mediat ing cellular trophic responses. The methods made use of an antisense o ligonucleotide that was prepared to the 5' terminus of APP and shown s pecifically to reduce the level of APP isoforms, 3. In sequential mixi ng experiments it was observed that the APP antisense oligonucleotide did not significantly modify the trophic response of PC12 cells pretre ated with nerve growth factor (NGF). However, pretreatment of cells wi th the antisense oligonucleotide diminished NGF-induced increases in c ellular size and neurite length. 4. These observations suggest that AP P may play a role in modulating the trophic response. The combined use of APP antisense oligonucleotides and neurotrophic agents may find cl inical utility in the treatment of Alzheimer-type dementia since it is known that NGF normally causes increases in APP levels.