Reprint of "Ganglioside lipids accelerate α-synuclein amyloid formation".

Authors:
Ricardo Gaspar
Ricardo Gaspar
From the Departments of Physical Chemistry
Ulrich Weininger
Ulrich Weininger
Center for Molecular Protein Science
Sara Linse
Sara Linse
Lund University
Sweden
Emma Sparr
Emma Sparr
Lund University
Sweden

Biochim Biophys Acta Proteins Proteom 2019 May 13;1867(5):508-518. Epub 2019 Mar 13.

Departments of Physical-Chemistry, Lund University, Sweden. Electronic address:

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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Source
http://dx.doi.org/10.1016/j.bbapap.2019.02.003DOI Listing
May 2019

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