%0 Journal Article
%T Synergistic influence of phosphorylation and metal ions on tau oligomer formation and coaggregation with ¦Á-synuclein at the single molecule level
%A N¨¹bling Georg
%A Bader Benedikt
%A Levin Johannes
%A Hildebrandt Jenna
%J Molecular Neurodegeneration
%D 2012
%I BioMed Central
%R 10.1186/1750-1326-7-35
%X Background Fibrillar amyloid-like deposits and co-deposits of tau and ¦Á-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 ¦Á-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 ¦Á-synuclein at the level of individual oligomers. We show that Al3+ at physiologically relevant concentrations and tau phosphorylation by GSK-3¦Â 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 ¦Á-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.
%K ¦Á-Synuclein
%K Metal ion
%K Oligomer
%K Phosphorylation
%K Tau
%K Iron
%K Aluminium
%K GSK-3 beta
%K Alzheimer¡¯s disease
%K Parkinson¡¯s disease
%U http://www.molecularneurodegeneration.com/content/7/1/35