Controlling Amyloid-β Peptide(1-42) Oligomerization and Toxicity by Fluorinated Nanoparticles

The amyloid-p peptide (A beta) 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 A beta 42. We show here that fluorinated and hydrogenated NPs with different abilities to change A beta 42 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 A beta 42 into an a-helical-enriched secondary structure also has antiapoptotic activity, thereby increasing the viability of cells treated with oligomeric species.