Activation of c-Fos contributes to amyloid beta-peptide-induced neurotoxicity

Amyloid beta peptide, a major component of Alzheimer's disease plaques, is directly toxic to various neuronal cell lines and primary neurons in culture. The mechanism underlying A beta neurotoxicity may include an increase in intracellular calcium and reactive oxygen species. In the present study, exposure of a mouse hippocampal cell line (HT-22) to the 25-35 peptide fragment of A beta (10 mu M) caused a rapid and sustained increase in nuclear c-Fos immunoreactivity. Inhibition of A beta-mediated c-Fos activation by c-fos antisense oligodeoxynucleotides (5 mu M) significantly protected against A beta toxicity as assessed by MTT assay. The signal transduction pathway for c-fos induction remains speculative, however, there seems to be a causal relationship between c-Fos transcription factor and A beta toxicity.