Ganglioside lipids accelerate α-synuclein amyloid formation
(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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- author
- Gaspar, Ricardo LU ; Pallbo, Jon LU ; Weininger, Ulrich LU ; Linse, Sara LU and Sparr, Emma LU
- organization
- publishing date
- 2018-10-01
- type
- 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
- pmid:30077783
- 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
- 2024-05-27 15:07:18
@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}},
doi = {{10.1016/j.bbapap.2018.07.004}},
volume = {{1866}},
year = {{2018}},
}