title: Rapid cellular uptake of Alzheimer amyloid betaA4 peptide by cultured human neuroblastoma cells.
abstract: Cerebral deposition of betaA4 (beta-amyloid) peptide is a major pathological feature of Alzheimer's disease. Although the mechanism of betaA4 production from cells has been investigated extensively, so far little is known about the catabolism of the peptide. We report here that the human neuroblastoma cell line SH-SY5Y can rapidly clear betaA4 in the culture medium. The clearance was not due to the degradation by extracellularly released protease, but rather due to intracellular degradation after cellular uptake. This clearance activity was specific to SH-SY5Y cells among several cell types examined. Some of the betaA4-derived peptides lacking the N-terminal part of the molecule were not catabolized, suggesting a specific interaction between the cells and betaA4. Although most of the peptide was degraded after uptake, small amounts of peptide were accumulated in insoluble fractions of the cells and remained stable for several days. These observations suggest that this uptake-degradation activity may contribute to AD pathogenesis in two different ways: either to prevent the amyloid deposition by reducing extracellular betaA4 concentrations, or to promote the deposition by producing insoluble seeds for amyloid formation.
authors.affiliation: Center for Molecular Biology Heidelberg (ZMBH), University of Heidelberg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Ida
authors.forename: C L
authors.initials: CL
authors.lastname: Masters
authors.forename: K
authors.initials: K
authors.lastname: Beyreuther
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D003470:Culture Media; D006801:Humans; D007700:Kinetics; D009447:Neuroblastoma; D009474:Neurons / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D016229:Amyloid beta-Peptides; D003470:Culture Media; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)