Modulation of aggregate size- and shape-distributions of the amyloid-β peptide by a designed β-sheet breaker

Luitgard Nagel-Steger, Borries Demeler, Wolfgang Meyer-Zaika, Katrin Hochdörffer, Thomas Schrader, Dieter Willbold

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

A peptide with 42 amino acid residues (Aβ42) plays a key role in the pathogenesis of the Alzheimer's disease. It is highly prone to self aggregation leading to the formation of fibrils which are deposited in amyloid plaques in the brain of diseased individuals. In our study we established a method to analyze the aggregation behavior of the Aβ peptide with a combination of sedimentation velocity centrifugation and enhanced data evaluation software as implemented in the software package UltraScan. Important information which becomes accessible by this methodology is the s-value distribution and concomitantly also the shape-distribution of the Aβ peptide aggregates generated by self-association. With this method we characterized the aggregation modifying effect of a designed bsheet breaker molecule. This compound is built from three head-to-tail connected aminopyrazole moieties and represents a derivative of the already described Tripyrazole. By addition of this compound to a solution of the Aβ42 peptide the maximum of the s-value distribution was clearly shifted to smaller s-values as compared to solutions where only the vehicle DMSO was added. This shift to smaller s-values was stable for at least 7 days. The information about size- and shape-distributions present in aggregated Aβ42 solutions was confirmed by transmission electron microscopy and by measurement of amyloid formation by thioflavin T fluorescence.

Original languageEnglish (US)
Pages (from-to)415-422
Number of pages8
JournalEuropean Biophysics Journal
Volume39
Issue number3
DOIs
StatePublished - Feb 2010

Fingerprint

Amyloid
Peptides
Software
Amyloid Plaques
Brain Diseases
Dimethyl Sulfoxide
Transmission Electron Microscopy
Centrifugation
Alzheimer Disease
Fluorescence
Amino Acids

Keywords

  • Aggregation inhibitor
  • Alzheimer's disease
  • Amyloid β
  • Peptide
  • Sedimentation velocity centrifugation
  • Thioflavin T
  • Transmission electron microscopy

ASJC Scopus subject areas

  • Biophysics
  • Medicine(all)

Cite this

Nagel-Steger, L., Demeler, B., Meyer-Zaika, W., Hochdörffer, K., Schrader, T., & Willbold, D. (2010). Modulation of aggregate size- and shape-distributions of the amyloid-β peptide by a designed β-sheet breaker. European Biophysics Journal, 39(3), 415-422. https://doi.org/10.1007/s00249-009-0416-2

Modulation of aggregate size- and shape-distributions of the amyloid-β peptide by a designed β-sheet breaker. / Nagel-Steger, Luitgard; Demeler, Borries; Meyer-Zaika, Wolfgang; Hochdörffer, Katrin; Schrader, Thomas; Willbold, Dieter.

In: European Biophysics Journal, Vol. 39, No. 3, 02.2010, p. 415-422.

Research output: Contribution to journalArticle

Nagel-Steger, L, Demeler, B, Meyer-Zaika, W, Hochdörffer, K, Schrader, T & Willbold, D 2010, 'Modulation of aggregate size- and shape-distributions of the amyloid-β peptide by a designed β-sheet breaker', European Biophysics Journal, vol. 39, no. 3, pp. 415-422. https://doi.org/10.1007/s00249-009-0416-2
Nagel-Steger, Luitgard ; Demeler, Borries ; Meyer-Zaika, Wolfgang ; Hochdörffer, Katrin ; Schrader, Thomas ; Willbold, Dieter. / Modulation of aggregate size- and shape-distributions of the amyloid-β peptide by a designed β-sheet breaker. In: European Biophysics Journal. 2010 ; Vol. 39, No. 3. pp. 415-422.
@article{87b207d7c57f4cabb504b1f721831330,
title = "Modulation of aggregate size- and shape-distributions of the amyloid-β peptide by a designed β-sheet breaker",
abstract = "A peptide with 42 amino acid residues (Aβ42) plays a key role in the pathogenesis of the Alzheimer's disease. It is highly prone to self aggregation leading to the formation of fibrils which are deposited in amyloid plaques in the brain of diseased individuals. In our study we established a method to analyze the aggregation behavior of the Aβ peptide with a combination of sedimentation velocity centrifugation and enhanced data evaluation software as implemented in the software package UltraScan. Important information which becomes accessible by this methodology is the s-value distribution and concomitantly also the shape-distribution of the Aβ peptide aggregates generated by self-association. With this method we characterized the aggregation modifying effect of a designed bsheet breaker molecule. This compound is built from three head-to-tail connected aminopyrazole moieties and represents a derivative of the already described Tripyrazole. By addition of this compound to a solution of the Aβ42 peptide the maximum of the s-value distribution was clearly shifted to smaller s-values as compared to solutions where only the vehicle DMSO was added. This shift to smaller s-values was stable for at least 7 days. The information about size- and shape-distributions present in aggregated Aβ42 solutions was confirmed by transmission electron microscopy and by measurement of amyloid formation by thioflavin T fluorescence.",
keywords = "Aggregation inhibitor, Alzheimer's disease, Amyloid β, Peptide, Sedimentation velocity centrifugation, Thioflavin T, Transmission electron microscopy",
author = "Luitgard Nagel-Steger and Borries Demeler and Wolfgang Meyer-Zaika and Katrin Hochd{\"o}rffer and Thomas Schrader and Dieter Willbold",
year = "2010",
month = "2",
doi = "10.1007/s00249-009-0416-2",
language = "English (US)",
volume = "39",
pages = "415--422",
journal = "European Biophysics Journal",
issn = "0175-7571",
publisher = "Springer Verlag",
number = "3",

}

TY - JOUR

T1 - Modulation of aggregate size- and shape-distributions of the amyloid-β peptide by a designed β-sheet breaker

AU - Nagel-Steger, Luitgard

AU - Demeler, Borries

AU - Meyer-Zaika, Wolfgang

AU - Hochdörffer, Katrin

AU - Schrader, Thomas

AU - Willbold, Dieter

PY - 2010/2

Y1 - 2010/2

N2 - A peptide with 42 amino acid residues (Aβ42) plays a key role in the pathogenesis of the Alzheimer's disease. It is highly prone to self aggregation leading to the formation of fibrils which are deposited in amyloid plaques in the brain of diseased individuals. In our study we established a method to analyze the aggregation behavior of the Aβ peptide with a combination of sedimentation velocity centrifugation and enhanced data evaluation software as implemented in the software package UltraScan. Important information which becomes accessible by this methodology is the s-value distribution and concomitantly also the shape-distribution of the Aβ peptide aggregates generated by self-association. With this method we characterized the aggregation modifying effect of a designed bsheet breaker molecule. This compound is built from three head-to-tail connected aminopyrazole moieties and represents a derivative of the already described Tripyrazole. By addition of this compound to a solution of the Aβ42 peptide the maximum of the s-value distribution was clearly shifted to smaller s-values as compared to solutions where only the vehicle DMSO was added. This shift to smaller s-values was stable for at least 7 days. The information about size- and shape-distributions present in aggregated Aβ42 solutions was confirmed by transmission electron microscopy and by measurement of amyloid formation by thioflavin T fluorescence.

AB - A peptide with 42 amino acid residues (Aβ42) plays a key role in the pathogenesis of the Alzheimer's disease. It is highly prone to self aggregation leading to the formation of fibrils which are deposited in amyloid plaques in the brain of diseased individuals. In our study we established a method to analyze the aggregation behavior of the Aβ peptide with a combination of sedimentation velocity centrifugation and enhanced data evaluation software as implemented in the software package UltraScan. Important information which becomes accessible by this methodology is the s-value distribution and concomitantly also the shape-distribution of the Aβ peptide aggregates generated by self-association. With this method we characterized the aggregation modifying effect of a designed bsheet breaker molecule. This compound is built from three head-to-tail connected aminopyrazole moieties and represents a derivative of the already described Tripyrazole. By addition of this compound to a solution of the Aβ42 peptide the maximum of the s-value distribution was clearly shifted to smaller s-values as compared to solutions where only the vehicle DMSO was added. This shift to smaller s-values was stable for at least 7 days. The information about size- and shape-distributions present in aggregated Aβ42 solutions was confirmed by transmission electron microscopy and by measurement of amyloid formation by thioflavin T fluorescence.

KW - Aggregation inhibitor

KW - Alzheimer's disease

KW - Amyloid β

KW - Peptide

KW - Sedimentation velocity centrifugation

KW - Thioflavin T

KW - Transmission electron microscopy

UR - http://www.scopus.com/inward/record.url?scp=77950552292&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77950552292&partnerID=8YFLogxK

U2 - 10.1007/s00249-009-0416-2

DO - 10.1007/s00249-009-0416-2

M3 - Article

C2 - 19238376

AN - SCOPUS:77950552292

VL - 39

SP - 415

EP - 422

JO - European Biophysics Journal

JF - European Biophysics Journal

SN - 0175-7571

IS - 3

ER -