Randomization of amyloid-β-peptide(1-42) conformation by sulfonated and sulfated nanoparticles reduces aggregation and cytotoxicity.

Ana M Saraiva, Isabel Cardoso, Maria João Saraiva, Klaus Tauer, M Carmo Pereira, Manuel A N Coelho, Helmuth Möhwald, Gerald Brezesinski

Index: Macromol. Biosci. 10 , 1152-1163, (2010)

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Abstract

The amyloid-β peptide (Aβ) plays a central role in the mechanism of Alzheimer's disease, being the main constituent of the plaque deposits found in AD brains. Aβ amyloid formation and deposition are due to a conformational switching to a β-enriched secondary structure. Our strategy to inhibit Aβ aggregation involves the re-conversion of Aβ conformation by adsorption to nanoparticles. NPs were synthesized by sulfonation and sulfation of polystyrene, leading to microgels and latexes. Both polymeric nanostructures affect the conformation of Aβ inducing an unordered state. Oligomerization was delayed and cytotoxicity reduced. The proper balance between hydrophilic moieties and hydrophobic chains seems to be an essential feature of effective NPs.