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@ARTICLE{Akoury:148122,
author = {Akoury, E. and Gajda, M. J. and Pickhardt, M. and Biernat,
J. and Pornsuwan, S. and Griesinger, Ch. and Mandelkow, E.
and Zweckstetter, M. and DESY},
title = {{I}nhibition of tau filament formation by conformational
modulation},
journal = {Journal of the American Chemical Society},
volume = {135},
issn = {0002-7863},
address = {Washington, DC},
publisher = {American Chemical Society},
reportid = {PHPPUBDB-26150},
pages = {2853-2862},
year = {2013},
abstract = {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.},
cin = {HASYLAB / MPG / EMBL},
ddc = {540},
cid = {$I:(DE-H253)HASYLAB_-2012_-20130307$ /
$I:(DE-H253)MPG_-2012_-20120307$ /
$I:(DE-H253)EMBL_-2012_-20130307$},
pnm = {DORIS Beamline D1.2 (POF2-54G13)},
pid = {G:(DE-H253)POF2-D1.2-20130405},
experiment = {EXP:(DE-H253)D-D1.2-20150101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:23360400},
UT = {WOS:000315373000066},
doi = {10.1021/ja312471h},
url = {https://bib-pubdb1.desy.de/record/148122},
}