title: Activation of c-Fos contributes to amyloid beta-peptide-induced neurotoxicity.
abstract: 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 microM) 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 microM) 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.
authors.affiliation: Physiologisches Institut der Universität Heidelberg, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Gillardon
authors.forename: T
authors.initials: T
authors.lastname: Skutella
authors.forename: E
authors.initials: E
authors.lastname: Uhlmann
authors.forename: F
authors.initials: F
authors.lastname: Holsboer
authors.forename: M
authors.initials: M
authors.lastname: Zimmermann
authors.forename: C
authors.initials: C
authors.lastname: Behl
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D007150:Immunohistochemistry; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects*; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis
chemical_list: D016229:Amyloid beta-Peptides; D016760:Proto-Oncogene Proteins c-fos