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Molecular Neurodegeneration
Published in: Molecular Neurodegeneration 1/2012

Open Access 01-12-2012 | Research article

Synergistic influence of phosphorylation and metal ions on tau oligomer formation and coaggregation with α-synuclein at the single molecule level

Authors: Georg Nübling, Benedikt Bader, Johannes Levin, Jenna Hildebrandt, Hans Kretzschmar, Armin Giese

Published in: Molecular Neurodegeneration | Issue 1/2012

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Abstract

Background

Fibrillar amyloid-like deposits and co-deposits of tau and α-synuclein are found in several common neurodegenerative diseases. Recent evidence indicates that small oligomers are the most relevant toxic aggregate species. While tau fibril formation is well-characterized, factors influencing tau oligomerization and molecular interactions of tau and α-synuclein are not well understood.

Results

We used a novel approach applying confocal single-particle fluorescence to investigate the influence of tau phosphorylation and metal ions on tau oligomer formation and its coaggregation with α-synuclein at the level of individual oligomers. We show that Al3+ at physiologically relevant concentrations and tau phosphorylation by GSK-3β exert synergistic effects on the formation of a distinct SDS-resistant tau oligomer species even at nanomolar protein concentration. Moreover, tau phosphorylation and Al3+ as well as Fe3+ enhanced both formation of mixed oligomers and recruitment of α-synuclein in pre-formed tau oligomers.

Conclusions

Our findings provide a new perspective on interactions of tau phosphorylation, metal ions, and the formation of potentially toxic oligomer species, and elucidate molecular crosstalks between different aggregation pathways involved in neurodegeneration.
Appendix
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Metadata
Title
Synergistic influence of phosphorylation and metal ions on tau oligomer formation and coaggregation with α-synuclein at the single molecule level
Authors
Georg Nübling
Benedikt Bader
Johannes Levin
Jenna Hildebrandt
Hans Kretzschmar
Armin Giese
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2012
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/1750-1326-7-35

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