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On the Cluster Formation of α-Synuclein Fibrils

Dubackic, Marija LU ; Idini, Ilaria LU ; Lattanzi, Veronica LU ; Liu, Yun ; Martel, Anne ; Terry, Ann LU ; Haertlein, Michael ; Devos, Juliette M. ; Jackson, Andrew LU and Sparr, Emma LU , et al. (2021) In Frontiers in Molecular Biosciences 8.
Abstract

The dense accumulation of α-Synuclein fibrils in neurons is considered to be strongly associated with Parkinson’s disease. These intracellular inclusions, called Lewy bodies, also contain significant amounts of lipids. To better understand such accumulations, it should be important to study α-Synuclein fibril formation under conditions where the fibrils lump together, mimicking what is observed in Lewy bodies. In the present study, we have therefore investigated the overall structural arrangements of α-synuclein fibrils, formed under mildly acidic conditions, pH = 5.5, in pure buffer or in the presence of various model membrane systems, by means of small-angle neutron scattering (SANS). At this pH, α-synuclein fibrils are colloidally... (More)

The dense accumulation of α-Synuclein fibrils in neurons is considered to be strongly associated with Parkinson’s disease. These intracellular inclusions, called Lewy bodies, also contain significant amounts of lipids. To better understand such accumulations, it should be important to study α-Synuclein fibril formation under conditions where the fibrils lump together, mimicking what is observed in Lewy bodies. In the present study, we have therefore investigated the overall structural arrangements of α-synuclein fibrils, formed under mildly acidic conditions, pH = 5.5, in pure buffer or in the presence of various model membrane systems, by means of small-angle neutron scattering (SANS). At this pH, α-synuclein fibrils are colloidally unstable and aggregate further into dense clusters. SANS intensities show a power law dependence on the scattering vector, q, indicating that the clusters can be described as mass fractal aggregates. The experimentally observed fractal dimension was d = 2.6 ± 0.3. We further show that this fractal dimension can be reproduced using a simple model of rigid-rod clusters. The effect of dominatingly attractive fibril-fibril interactions is discussed within the context of fibril clustering in Lewy body formation.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
alpha-synuclein, amyloid fibril, fractal cluster, Lewy bodies (LB), rigid-rod cluster modeling, small-angle neutron scattering (SANS)
in
Frontiers in Molecular Biosciences
volume
8
article number
768004
publisher
Frontiers Media S. A.
external identifiers
  • pmid:34738016
  • scopus:85118376671
ISSN
2296-889X
DOI
10.3389/fmolb.2021.768004
language
English
LU publication?
yes
additional info
Publisher Copyright: © Copyright © 2021 Dubackic, Idini, Lattanzi, Liu, Martel, Terry, Haertlein, Devos, Jackson, Sparr, Linse and Olsson.
id
b3fd6373-646a-4355-9709-a6da4985f130
date added to LUP
2021-11-22 12:45:35
date last changed
2024-03-23 14:13:21
@article{b3fd6373-646a-4355-9709-a6da4985f130,
  abstract     = {{<p>The dense accumulation of α-Synuclein fibrils in neurons is considered to be strongly associated with Parkinson’s disease. These intracellular inclusions, called Lewy bodies, also contain significant amounts of lipids. To better understand such accumulations, it should be important to study α-Synuclein fibril formation under conditions where the fibrils lump together, mimicking what is observed in Lewy bodies. In the present study, we have therefore investigated the overall structural arrangements of α-synuclein fibrils, formed under mildly acidic conditions, pH = 5.5, in pure buffer or in the presence of various model membrane systems, by means of small-angle neutron scattering (SANS). At this pH, α-synuclein fibrils are colloidally unstable and aggregate further into dense clusters. SANS intensities show a power law dependence on the scattering vector, q, indicating that the clusters can be described as mass fractal aggregates. The experimentally observed fractal dimension was d = 2.6 ± 0.3. We further show that this fractal dimension can be reproduced using a simple model of rigid-rod clusters. The effect of dominatingly attractive fibril-fibril interactions is discussed within the context of fibril clustering in Lewy body formation.</p>}},
  author       = {{Dubackic, Marija and Idini, Ilaria and Lattanzi, Veronica and Liu, Yun and Martel, Anne and Terry, Ann and Haertlein, Michael and Devos, Juliette M. and Jackson, Andrew and Sparr, Emma and Linse, Sara and Olsson, Ulf}},
  issn         = {{2296-889X}},
  keywords     = {{alpha-synuclein; amyloid fibril; fractal cluster; Lewy bodies (LB); rigid-rod cluster modeling; small-angle neutron scattering (SANS)}},
  language     = {{eng}},
  month        = {{10}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Molecular Biosciences}},
  title        = {{On the Cluster Formation of α-Synuclein Fibrils}},
  url          = {{http://dx.doi.org/10.3389/fmolb.2021.768004}},
  doi          = {{10.3389/fmolb.2021.768004}},
  volume       = {{8}},
  year         = {{2021}},
}