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Ganglioside lipids accelerate α-synuclein amyloid formation

Gaspar, Ricardo LU ; Pallbo, Jon LU ; Weininger, Ulrich LU ; Linse, Sara LU and Sparr, Emma LU (2018) In Biochimica et Biophysica Acta - Proteins and Proteomics 1866(10). p.1062-1072
Abstract

The deposition of α-synuclein fibrils is one hallmark of Parkinson's disease. Here, we investigate how ganglioside lipids, present in high amounts in neurons and exosomes, influence the aggregation kinetics of α-synuclein. Gangliosides, as well as, other anionic lipid species with small or large headgroups were found to induce conformational changes of α-synuclein monomers and catalyse their aggregation at mildly acidic conditions. Although the extent of this catalytic effect was slightly higher for gangliosides, the results imply that charge interactions are more important than headgroup chemistry in triggering aggregation. In support of this idea, uncharged lipids with large headgroups were not found to induce any conformational... (More)

The deposition of α-synuclein fibrils is one hallmark of Parkinson's disease. Here, we investigate how ganglioside lipids, present in high amounts in neurons and exosomes, influence the aggregation kinetics of α-synuclein. Gangliosides, as well as, other anionic lipid species with small or large headgroups were found to induce conformational changes of α-synuclein monomers and catalyse their aggregation at mildly acidic conditions. Although the extent of this catalytic effect was slightly higher for gangliosides, the results imply that charge interactions are more important than headgroup chemistry in triggering aggregation. In support of this idea, uncharged lipids with large headgroups were not found to induce any conformational change and only weakly catalyse aggregation. Intriguingly, aggregation was also triggered by free ganglioside headgroups, while these caused no conformational change of α-synuclein monomers. Our data reveal that partially folded α-synuclein helical intermediates are not required species in triggering of α-synuclein aggregation.

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organization
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Contribution to journal
publication status
published
subject
in
Biochimica et Biophysica Acta - Proteins and Proteomics
volume
1866
issue
10
pages
11 pages
publisher
Elsevier
external identifiers
  • scopus:85051108265
ISSN
1570-9639
DOI
10.1016/j.bbapap.2018.07.004
language
English
LU publication?
yes
id
3895e20a-3343-45c5-bcdc-c36ce4a73306
date added to LUP
2018-08-15 08:29:53
date last changed
2019-10-15 06:43:24
@article{3895e20a-3343-45c5-bcdc-c36ce4a73306,
  abstract     = {<p>The deposition of α-synuclein fibrils is one hallmark of Parkinson's disease. Here, we investigate how ganglioside lipids, present in high amounts in neurons and exosomes, influence the aggregation kinetics of α-synuclein. Gangliosides, as well as, other anionic lipid species with small or large headgroups were found to induce conformational changes of α-synuclein monomers and catalyse their aggregation at mildly acidic conditions. Although the extent of this catalytic effect was slightly higher for gangliosides, the results imply that charge interactions are more important than headgroup chemistry in triggering aggregation. In support of this idea, uncharged lipids with large headgroups were not found to induce any conformational change and only weakly catalyse aggregation. Intriguingly, aggregation was also triggered by free ganglioside headgroups, while these caused no conformational change of α-synuclein monomers. Our data reveal that partially folded α-synuclein helical intermediates are not required species in triggering of α-synuclein aggregation.</p>},
  author       = {Gaspar, Ricardo and Pallbo, Jon and Weininger, Ulrich and Linse, Sara and Sparr, Emma},
  issn         = {1570-9639},
  language     = {eng},
  month        = {10},
  number       = {10},
  pages        = {1062--1072},
  publisher    = {Elsevier},
  series       = {Biochimica et Biophysica Acta - Proteins and Proteomics},
  title        = {Ganglioside lipids accelerate α-synuclein amyloid formation},
  url          = {http://dx.doi.org/10.1016/j.bbapap.2018.07.004},
  volume       = {1866},
  year         = {2018},
}