Dataset Information

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

ABSTRACT:

Background

Fibrillar amyloid-like deposits and co-deposits of tau and ?-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 ?-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 ?-synuclein at the level of individual oligomers. We show that Al3+ at physiologically relevant concentrations and tau phosphorylation by GSK-3? 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 ?-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.

SUBMITTER: Nubling G

PROVIDER: S-EPMC3472288 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Nübling Georg G Bader Benedikt B Levin Johannes J Hildebrandt Jenna J Kretzschmar Hans H Giese Armin A

Molecular neurodegeneration 20120723

<h4>Background</h4>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.<h4>Results</h4>We used a novel approach applying confocal single-particle fluorescence to inves ...[more]

PMID: 22824345

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