Ligand-induced flocculation of neurotoxic fibrillar aβ (1-42) by noncovalent crosslinking

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Aggregation of the amyloid-β (Aβ) peptides has a pivotal role in Alzheimer's disease (AD). Small molecules and short peptides/ peptidomimetics can exert their full protective effects against Aβ within a short time-frame, but the exact mechanism of action is unclear. Time-dependent NMR spectroscopic binding and replacement experiments were carried out for peptide LPFFD and thioflavine T (ThT) on neurotoxic fibrillar Aβ(1-42), which revealed transient binding behavior for both compounds, and complex time-dependent features in the replacement experiments. The results of particle size measurements through the use of diffuse light-scattering and transmission electron microscopy support the conclusions that the studied ligands induced interfibrillar association on a short timescale, which explains the NMR spectroscopic binding and replacement results. ζ-Potential measurements revealed a slightly increased electrostatic stability of the Aβ fibrils upon ligand binding; this suggests that the interfibrillar assembly is driven by specific noncovalent cross-linking interactions. A specific surface and mobility decrease due to the ligand-induced flocculation of the Aβ fibrils can explain the neuroprotective effects.

Original languageEnglish
Pages (from-to)748-757
Number of pages10
JournalChemBioChem
Volume9
Issue number5
DOIs
Publication statusPublished - Mar 25 2008

Fingerprint

Flocculation
Crosslinking
Ligands
Nuclear magnetic resonance
Peptidomimetics
Peptides
Neuroprotective Agents
Light transmission
Static Electricity
Transmission Electron Microscopy
Particle Size
Amyloid
Light scattering
Electrostatics
Alzheimer Disease
Agglomeration
Experiments
Particle size
Association reactions
Transmission electron microscopy

Keywords

  • Beta-amyloid peptides
  • Electron microscopy
  • Neurochemistry
  • NMR spectropy

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Medicine(all)

Cite this

Ligand-induced flocculation of neurotoxic fibrillar aβ (1-42) by noncovalent crosslinking. / Hetényi, A.; Fülöp, L.; Martinek, T.; Wéber, Edit; Soós, K.; Penke, B.

In: ChemBioChem, Vol. 9, No. 5, 25.03.2008, p. 748-757.

Research output: Contribution to journalArticle

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