001     148122
005     20250803045138.0
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024 7 _ |a 1520-5126
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024 7 _ |a 10.1021/ja312471h
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037 _ _ |a PHPPUBDB-26150
041 _ _ |a eng
082 _ _ |a 540
100 1 _ |a Akoury, E.
110 1 _ |a DESY
|b Experiments with synchrotron radiation
245 _ _ |a Inhibition of tau filament formation by conformational modulation
260 _ _ |a Washington, DC
|c 2013
|b American Chemical Society
300 _ _ |a 2853-2862
336 7 _ |a Journal Article
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440 _ 0 |a J. Am. Chem. Soc.
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|v 135
|y 7
|x 0002-7863
500 _ _ |3 Converted on 2013-05-30 10:06
500 _ _ |3 Converted on 2013-06-21 19:21
520 _ _ |a Antiaggregation drugs play an important role in therapeutic approaches for Alzheimer's disease. Although a large number of small molecules that inhibit the aggregation of the tau protein have been identified, little is known about their mode of action. Here, we reveal the mechanism and the nature of tau species that are generated by interaction of tau with the organic compound pthalocyanine tetrasulfonate (PcTS). We demonstrate that PcTS interferes with tau filament formation by targeting the protein into soluble oligomers. A combination of NMR spectroscopy, electron paramagnetic resonance, and small-angle X-ray scattering reveals that the soluble tau oligomers contain a dynamic, noncooperatively stabilized core with a diameter of 30-40 nm that is distinct from the core of tau filaments. Our results suggest that specific modulation of the conformation of tau is a viable strategy for reduction of pathogenic tau deposits.
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700 1 _ |a Gajda, M. J.
700 1 _ |a Pickhardt, M.
700 1 _ |a Biernat, J.
700 1 _ |a Pornsuwan, S.
700 1 _ |a Griesinger, Ch.
700 1 _ |a Mandelkow, E.
700 1 _ |a Zweckstetter, M.
773 _ _ |a 10.1021/ja312471h
|g Vol. 135, p. 2853-2862
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|v 135
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913 1 _ |b Struktur der Materie
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|l Forschung mit Photonen, Neutronen, Ionen
914 1 _ |a (c) American Chemical Society. Post Referee-Version 12 Monate gesperrt (bis Feb. 2014). Code P.
|y 2013
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