Synergistic influence of phosphorylation and metal ions on tau oligomer formation and coaggregation with α-synuclein at the single molecule level
<p>Abstract</p> <p>Background</p> <p>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 fi...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2012-07-01
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| Series: | Molecular Neurodegeneration |
| Subjects: | |
| Online Access: | http://www.molecularneurodegeneration.com/content/7/1/35 |
| _version_ | 1818751437331496960 |
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| author | Nübling Georg Bader Benedikt Levin Johannes Hildebrandt Jenna Kretzschmar Hans Giese Armin |
| author_facet | Nübling Georg Bader Benedikt Levin Johannes Hildebrandt Jenna Kretzschmar Hans Giese Armin |
| author_sort | Nübling Georg |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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 Al<sup>3+</sup> 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 Al<sup>3+</sup> as well as Fe<sup>3+</sup> enhanced both formation of mixed oligomers and recruitment of α-synuclein in pre-formed tau oligomers.</p> <p>Conclusions</p> <p>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.</p> |
| first_indexed | 2024-12-18T04:35:33Z |
| format | Article |
| id | doaj.art-73730f75ff35477c89e5617925d3dec4 |
| institution | Directory Open Access Journal |
| issn | 1750-1326 |
| language | English |
| last_indexed | 2024-12-18T04:35:33Z |
| publishDate | 2012-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Neurodegeneration |
| spelling | doaj.art-73730f75ff35477c89e5617925d3dec42022-12-21T21:20:52ZengBMCMolecular Neurodegeneration1750-13262012-07-01713510.1186/1750-1326-7-35Synergistic influence of phosphorylation and metal ions on tau oligomer formation and coaggregation with α-synuclein at the single molecule levelNübling GeorgBader BenediktLevin JohannesHildebrandt JennaKretzschmar HansGiese Armin<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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 Al<sup>3+</sup> 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 Al<sup>3+</sup> as well as Fe<sup>3+</sup> enhanced both formation of mixed oligomers and recruitment of α-synuclein in pre-formed tau oligomers.</p> <p>Conclusions</p> <p>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.</p>http://www.molecularneurodegeneration.com/content/7/1/35α-Synuclein, Metal ion, Oligomer, Phosphorylation, Tau, Iron, Aluminium, GSK-3 beta, Alzheimer’s diseaseParkinson’s disease |
| spellingShingle | Nübling Georg Bader Benedikt Levin Johannes Hildebrandt Jenna Kretzschmar Hans Giese Armin Synergistic influence of phosphorylation and metal ions on tau oligomer formation and coaggregation with α-synuclein at the single molecule level Molecular Neurodegeneration α-Synuclein, Metal ion, Oligomer, Phosphorylation, Tau, Iron, Aluminium, GSK-3 beta, Alzheimer’s disease Parkinson’s disease |
| title | Synergistic influence of phosphorylation and metal ions on tau oligomer formation and coaggregation with α-synuclein at the single molecule level |
| title_full | Synergistic influence of phosphorylation and metal ions on tau oligomer formation and coaggregation with α-synuclein at the single molecule level |
| title_fullStr | Synergistic influence of phosphorylation and metal ions on tau oligomer formation and coaggregation with α-synuclein at the single molecule level |
| title_full_unstemmed | Synergistic influence of phosphorylation and metal ions on tau oligomer formation and coaggregation with α-synuclein at the single molecule level |
| title_short | Synergistic influence of phosphorylation and metal ions on tau oligomer formation and coaggregation with α-synuclein at the single molecule level |
| title_sort | synergistic influence of phosphorylation and metal ions on tau oligomer formation and coaggregation with α synuclein at the single molecule level |
| topic | α-Synuclein, Metal ion, Oligomer, Phosphorylation, Tau, Iron, Aluminium, GSK-3 beta, Alzheimer’s disease Parkinson’s disease |
| url | http://www.molecularneurodegeneration.com/content/7/1/35 |
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