Ganglioside lipids accelerate α-synuclein amyloid formation

Ricardo Gaspar; Jon Pallbo; Ulrich Weininger; Sara Linse; Emma Sparr

doi:10.1016/j.bbapap.2018.07.004

Ganglioside lipids accelerate α-synuclein amyloid formation

Biochim Biophys Acta Proteins Proteom. 2018 Aug 2;1866(10):1062-1072. doi: 10.1016/j.bbapap.2018.07.004. Online ahead of print.

Authors

Ricardo Gaspar¹, Jon Pallbo², Ulrich Weininger³, Sara Linse⁴, Emma Sparr⁵

Affiliations

¹ Departments of Physical-Chemistry, Lund University, Sweden; Biochemistry and Structural Biology, Lund University, Sweden.
² Departments of Physical-Chemistry, Lund University, Sweden.
³ Institute of Physics, Martin-Luther-University Halle-Wittenberg, Germany.
⁴ Biochemistry and Structural Biology, Lund University, Sweden.
⁵ Departments of Physical-Chemistry, Lund University, Sweden. Electronic address: emma.sparr@fkem1.lu.se.

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 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.