title: Controlling amyloid-beta peptide(1-42) oligomerization and toxicity by fluorinated nanoparticles.
abstract: The amyloid-beta peptide (Abeta) is a major fibrillar component of neuritic plaques in Alzheimer's disease brains and is related to the pathogenesis of the disease. Soluble oligomers that precede fibril formation have been proposed as the main neurotoxic species that contributes to neurodegeneration and dementia. We hypothesize that oligomerization and cytotoxicity can be repressed by nanoparticles (NPs) that induce conformational changes in Abeta42. We show here that fluorinated and hydrogenated NPs with different abilities to change Abeta42 conformation influence oligomerization as assessed by atomic force microscopy, immunoblot and SDS-PAGE. Fluorinated NPs, which promote an increase in alpha-helical content, exert an antioligomeric effect, whereas hydrogenated analogues do not and lead to aggregation. Cytotoxicity assays confirmed our hypothesis by indicating that the conformational conversion of Abeta42 into an alpha-helical-enriched secondary structure also has antiapoptotic activity, thereby increasing the viability of cells treated with oligomeric species.
authors.affiliation: Interfaces Department, Max Planck Institute of Colloids and Interfaces, Wissenschaftspark Golm, 14476 Potsdam, Germany. saraiva@mpikg.mpg.de
authors.forename: Ana M
authors.initials: AM
authors.lastname: Saraiva
authors.forename: Isabel
authors.initials: I
authors.lastname: Cardoso
authors.forename: M Carmo
authors.initials: MC
authors.lastname: Pereira
authors.forename: Manuel A N
authors.initials: MA
authors.lastname: Coelho
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Saraiva
authors.forename: Helmuth
authors.initials: H
authors.lastname: Möhwald
authors.forename: Gerald
authors.initials: G
authors.lastname: Brezesinski
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000633:toxicity; D002151:Calorimetry; D045744:Cell Line, Tumor; D005461:Fluorine / Q000737:chemistry*; D006801:Humans; D018625:Microscopy, Atomic Force; D053758:Nanoparticles / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry* / Q000633:toxicity; D017433:Protein Structure, Secondary
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D005461:Fluorine