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Inhibition of Amyloid beta Protein Fibrillation by Polymeric Nanoparticles

Cabaleiro-Lago, Celia; Quinlan-Pluck, Fiona; Lynch, Iseult; Lindman, Stina LU ; Minogue, Aedin M.; Thulin, Eva LU ; Walsh, Dominic M.; Dawson, Kenneth A. and Linse, Sara LU (2008) In Journal of the American Chemical Society 130(46). p.15437-15443
Abstract
Copolymeric NiPAM:BAM nanoparticles of varying hydrophobicity were found to retard fibrillation of the Alzheimer's disease-associated amyloid beta protein (A beta). We found that these nanoparticles affect mainly the nucleation step of A beta fibrillation. The elongation step is largely unaffected by the particles, and once the M is nucleated, the fibrillation process occurs with the same rate as in the absence of nanoparticles. The extension of the lag phase for fibrillation of A beta is strongly dependent on both the amount and surface character of the nanoparticles. Surface plasmon resonance studies show that A beta binds to the nanoparticles and provide rate and equilibrium constants for the interaction. Numerical analysis of the... (More)
Copolymeric NiPAM:BAM nanoparticles of varying hydrophobicity were found to retard fibrillation of the Alzheimer's disease-associated amyloid beta protein (A beta). We found that these nanoparticles affect mainly the nucleation step of A beta fibrillation. The elongation step is largely unaffected by the particles, and once the M is nucleated, the fibrillation process occurs with the same rate as in the absence of nanoparticles. The extension of the lag phase for fibrillation of A beta is strongly dependent on both the amount and surface character of the nanoparticles. Surface plasmon resonance studies show that A beta binds to the nanoparticles and provide rate and equilibrium constants for the interaction. Numerical analysis of the kinetic data for fibrillation suggests that binding of monomeric A beta and prefibrillar oligomers to the nanoparticles prevents fibrillation. Moreover, we find that fibrillation of A beta initiated in the absence of nanoparticles can be reversed by addition of nanoparticles up to a particular time point before mature fibrils appear. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of the American Chemical Society
volume
130
issue
46
pages
15437 - 15443
publisher
The American Chemical Society
external identifiers
  • wos:000263311300047
  • scopus:56449124781
ISSN
1520-5126
DOI
10.1021/ja8041806
language
English
LU publication?
yes
id
3af8bb12-7a69-4de3-b691-feeba29f1016 (old id 1375571)
date added to LUP
2009-05-08 14:53:38
date last changed
2017-10-22 04:21:35
@article{3af8bb12-7a69-4de3-b691-feeba29f1016,
  abstract     = {Copolymeric NiPAM:BAM nanoparticles of varying hydrophobicity were found to retard fibrillation of the Alzheimer's disease-associated amyloid beta protein (A beta). We found that these nanoparticles affect mainly the nucleation step of A beta fibrillation. The elongation step is largely unaffected by the particles, and once the M is nucleated, the fibrillation process occurs with the same rate as in the absence of nanoparticles. The extension of the lag phase for fibrillation of A beta is strongly dependent on both the amount and surface character of the nanoparticles. Surface plasmon resonance studies show that A beta binds to the nanoparticles and provide rate and equilibrium constants for the interaction. Numerical analysis of the kinetic data for fibrillation suggests that binding of monomeric A beta and prefibrillar oligomers to the nanoparticles prevents fibrillation. Moreover, we find that fibrillation of A beta initiated in the absence of nanoparticles can be reversed by addition of nanoparticles up to a particular time point before mature fibrils appear.},
  author       = {Cabaleiro-Lago, Celia and Quinlan-Pluck, Fiona and Lynch, Iseult and Lindman, Stina and Minogue, Aedin M. and Thulin, Eva and Walsh, Dominic M. and Dawson, Kenneth A. and Linse, Sara},
  issn         = {1520-5126},
  language     = {eng},
  number       = {46},
  pages        = {15437--15443},
  publisher    = {The American Chemical Society},
  series       = {Journal of the American Chemical Society},
  title        = {Inhibition of Amyloid beta Protein Fibrillation by Polymeric Nanoparticles},
  url          = {http://dx.doi.org/10.1021/ja8041806},
  volume       = {130},
  year         = {2008},
}