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.
Saraiva
Ana M
AM
Max Planck Institute of Colloids and Interfaces, Wissenschaftspark Golm, Potsdam, Germany. saraiva@mpikg.mpg.de
Cardoso
Isabel
I
Saraiva
Maria João
MJ
Tauer
Klaus
K
Pereira
M Carmo
MC
Coelho
Manuel A N
MA
Möhwald
Helmuth
H
Brezesinski
Gerald
G
D000544:Alzheimer Disease / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000235:genetics / Q000633:toxicity* / Q000648:ultrastructure; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D005782:Gels / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000633:toxicity* / Q000648:ultrastructure; D011487:Protein Conformation; D013501:Surface-Active Agents / Q000737:chemistry
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D005782:Gels; D010446:Peptide Fragments; D013501:Surface-Active Agents; C075222:amyloid beta-protein (1-42)