Rapid aggregation and assembly in aqueous solution of A beta (25-35) peptide.
The highly toxic A beta (25-35) is a peculiar peptide that differs from all the other commonly studied beta-amyloid peptides because of its extremely rapid aggregation properties and enhanced neurotoxicity. We investigated A beta (25-35) aggregation in H2O at pH 3.0 and at pH 7.4 by means of in-solution analyses. Adopting UV spectroscopy, Congo red spectrophotometry and thioflavin T fluorimetry, we were able to quantify, in water, the very fast assembling time necessary for A beta (25-35) to form stable insoluble aggregates and their ability to seed or not seed fibril growth. Our quantitative results, which confirm a very rapid assembly leading to stable insoluble aggregates of A beta (25-35) only when incubated at pH 7.4, might be helpful for designing novel aggregation inhibitors and to shed light on the in vivo environment in which fibril formation takes place.
Millucci
Lia
L
Department of Molecular Biology, University of Siena, Siena, Italy.
Raggiaschi
Roberto
R
Franceschini
Davide
D
Terstappen
Georg
G
Santucci
Annalisa
A
D016229:Amyloid beta-Peptides / Q000737:chemistry*; D052160:Benzothiazoles; D003224:Congo Red / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D015233:Models, Statistical; D009391:Nephelometry and Turbidimetry / Q000379:methods; D009498:Neurotoxins / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D013050:Spectrometry, Fluorescence / Q000379:methods; D013056:Spectrophotometry, Ultraviolet / Q000379:methods; D013844:Thiazoles / Q000737:chemistry; D013997:Time Factors; D014867:Water / Q000737:chemistry
D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D009498:Neurotoxins; D010446:Peptide Fragments; D010455:Peptides; D013844:Thiazoles; C074636:amyloid beta-protein (25-35); D014867:Water; C009462:thioflavin T; D003224:Congo Red