Randomization of Amyloid-β-Peptide(1-42) Conformation by Sulfonated and Sulfated Nanoparticles Reduces Aggregation and Cytotoxicity

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. Sulfonated and sulfated polystyrene nanoparticles interact with Aβ peptide inducing randomization of its structure. As a consequence, the oligomerization process is disturbed and the peptide induced toxicity to neuroblastoma cells is reduced. These results comprise attractive achievements for the development of approaches for the study and therapy of protein misfolding diseases.