Messenger RNAs of beta-amyloid precursor protein and prion protein are regulated by nerve growth factor in PC12 cells

The effect of the neurotrophic factor NGF on the expression of two genes involved in the accumulation of amyloid deposits in neurodegenerative disorders was studied in a clonal cell line, PC12. Use of hybridization methods showed that NGF increased the cellular pool of the mRNA of the prion protein, a macromolecule known to generate fibrillary aggregates in the brain of scrapie-infected animals. Maximal levels of prion mRNA were obtained after 7 days of treatment, but a significant increase was already detectable after 48 hr of exposure to NGF. In contrast, the factor did not increase the cellular content of the transcripts coding for the precursor of the beta-amyloid peptide (APP), which participates in the formation of neuritic plaques in human brains affected by Alzheimer's disease. However, NGF caused a drop in the molecular weight of that mRNA. This change, which is likely to result from a loss of 100-200 bp, was already detected after 24 hr of treatment. These results indicate that NGF induces in target neuronal cells a quantitative and a qualitative modification of the transcription products encoding two different amyloid precursor proteins.