Disturbance in cholesterol homeostasis appears to be an important factor in the pathogenesis of neurodegenerative disorders. The aim of the present study was to investigate sterol regulatory element binding protein (SREBP) levels in the nuclear extracts of human neuroblastoma cells and the possible interaction of beta-amyloid peptide (A beta) and cholesterol with this transcription factor. In this study, cultured human neuroblastoma cells (SHSY-5Y) were incubated in serum-deprived media in the presence or absence of A beta((25-35)) (1 mu M) or cholesterol (300 mu M) for 24 h. Nuclear extracts were subjected to SDS-PAGE, and SREBP cleavage product (68 kDa) was detected by immunoblotting. SREBP levels were elevated in the cells incubated 24 h in serum-deprived experimental media and were attenuated by A beta or cholesterol-supplementation. It is likely that the ability of A beta to release cholesterol into the medium and downregulate SREBP is due to a feedback mechanism.