title: Aβ1-16 can aggregate and induce the production of reactive oxygen species, nitric oxide, and inflammatory cytokines.
abstract: Amyloid-β (Aβ40/42) aggregates containing the cross-β-sheet structure are associated with the pathogenesis of Alzheimer's disease (AD). It is generally accepted that the N-terminal peptide of Aβ40/42, Aβ1-16, does not aggregate, and is not cytotoxic. However, we here show that Aβ1-16 can aggregate, and form cytotoxic aggregates containing β-turns and regular non-amyloid β-sheet structures. Factors such as pH, ionic strength, and agitation were found to influence Aβ1-16 aggregation, and the amino acid residues Asp1, His6, Ser8, and Val12 in Aβ1-16 may play a role in this aggregation. Our MTT results showed that Aβ1-16 monomers or oligomers were toxic to SH-SY5Y cells, but Aβ1-16 fibrils exhibited less cytotoxicity. Our studies also indicate that Aβ1-16 aggregates can increase the formation of reactive oxygen species and nitric oxide, induce the loss of calcium homeostasis, and incur the microglial production of TNF-α and IL-4. Thus, our findings suggest that Aβ1-16 may contribute to AD pathogenesis.
authors.affiliation: Tsinghua University, School of Medicine, Haidian District, Beijing, China.
authors.forename: Xue-ting
authors.initials: XT
authors.lastname: Du
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Yu-jiong
authors.initials: YJ
authors.lastname: Wang
authors.forename: Maria
authors.initials: M
authors.lastname: Andreasen
authors.forename: Da-wei
authors.initials: DW
authors.lastname: Zhan
authors.forename: Ying
authors.initials: Y
authors.lastname: Feng
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.forename: Daniel
authors.initials: D
authors.lastname: Otzen
authors.forename: Di
authors.initials: D
authors.lastname: Xue
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Rui-tian
authors.initials: RT
authors.lastname: Liu
mesh_terms: D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D018836:Inflammation Mediators / Q000138:chemical synthesis / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000633:toxicity*; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017382:Reactive Oxygen Species / Q000138:chemical synthesis / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016207:Cytokines; D018836:Inflammation Mediators; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C433241:amyloid beta-protein (1-16); D009569:Nitric Oxide