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Rapid aggregation and assembly in aqueous solution of Aβ (25–35) peptide

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Abstract

The highly toxic Aβ(25–35) is a peculiar peptide that differs from all the other commonly studied β-amyloid peptides because of its extremely rapid aggregation properties and enhanced neurotoxicity. We investigated Aβ(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 Aβ(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 Aβ(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.

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Abbreviations

AD:

Alzheimer disease

DMSO:

dimethyl sulphoxide

HFIP:

hexafluorisopropanol

IBM:

inclusion body myositis

NCC:

nucleated conformational conversion’

OD:

optical density

PBS:

phosphate buffered saline

pI:

isoelectric point

SDS:

sodium dodecyl sulphate

TFA:

trifluoroacetic acid

Th-T:

thioflavin-T

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Authors and Affiliations

  1. Department of Molecular Biology, University of Siena, Siena, Italy

    Lia Millucci & Annalisa Santucci

  2. SienaBiotech, via Fiorentina 1, 53100, Siena, Italy

    Roberto Raggiaschi, Davide Franceschini & Georg Terstappen

Authors
  1. Lia Millucci
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  2. Roberto Raggiaschi
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  3. Davide Franceschini
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  4. Georg Terstappen
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  5. Annalisa Santucci
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Correspondence to Annalisa Santucci.

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Millucci, L., Raggiaschi, R., Franceschini, D. et al. Rapid aggregation and assembly in aqueous solution of Aβ (25–35) peptide. J Biosci 34, 293–303 (2009). https://doi.org/10.1007/s12038-009-0033-3

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  • DOI: https://doi.org/10.1007/s12038-009-0033-3

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