title: Effects of polyamino acids and polyelectrolytes on amyloid β fibril formation.
abstract: The fibril formation of the neurodegenerative peptide amyloid β (Aβ42) is sensitive to solution conditions, and several proteins and peptides have been found to retard the process. Aβ42 fibril formation was followed with ThT fluorescence in the presence of polyamino acids (poly-glutamic acid, poly-lysine, and poly-threonine) and other polymers (poly(acrylic acid), poly(ethylenimine), and poly(diallyldimethylammonium chloride). An accelerating effect on the Aβ42 aggregation process is observed from all positively charged polymers, while no effect is seen from the negative or neutral polymers. The accelerating effect is dependent on the concentration of positive polymer in a highly reproducible manner. Acceleration is observed from a 1:500 polymer to Aβ42 weight ratio and up. Polyamino acids and the other polymers exert quantitatively the same effect at the same concentrations based on weight. Fibrils are formed in all cases as verified by transmission electron microscopy. The concentrations of polymers required for acceleration are too low to affect the Aβ42 aggregation process through increased ionic strength or molecular crowding effects. Instead, the acceleration seems to arise from the locally increased Aβ42 concentration near the polymers, which favors association and affects the electrostatic environment of the peptide.
authors: Division of Biochemistry and Structural Biology, Lund University , P.O. Box 124, SE 221 00 Lund, Sweden.
authors: Anna
authors: A
authors: Assarsson
authors: Sara
authors: S
authors: Linse
authors: Celia
authors: C
authors: Cabaleiro-Lago
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000648:ultrastructure; D007700:Kinetics; D046529:Microscopy, Electron, Transmission; D008970:Molecular Weight; D010446:Peptide Fragments / Q000737:chemistry* / Q000648:ultrastructure; D011094:Polyethyleneimine / Q000737:chemistry*; D011095:Polyethylenes / Q000737:chemistry*; D011099:Polyglutamic Acid / Q000737:chemistry*; D011107:Polylysine / Q000737:chemistry*; D058105:Polymerization; D066329:Protein Aggregates; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D055672:Static Electricity; D013912:Threonine / Q000737:chemistry*
chemical_list: D000180:Acrylic Resins; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011095:Polyethylenes; D066329:Protein Aggregates; D000644:Quaternary Ammonium Compounds; C075222:amyloid beta-protein (1-42); D011107:Polylysine; D011099:Polyglutamic Acid; C041004:poly-N,N-dimethyl-N,N-diallylammonium chloride; D013912:Threonine; C006903:carbopol 940; D011094:Polyethyleneimine