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@ARTICLE{Prince:256516,
author = {Prince, Prabhu Rajaiah and Hochmair, Janine and Brognaro,
Hévila and Gevorgyan, Susanna and Franck, Maximilian and
Schubert, Robin and Lorenzen, Kristina and Yazici, Selin and
Mandelkow, Eckhard and Wegmann, Susanne and Betzel,
Christian},
title = {{I}nitiation and modulation of {T}au protein phase
separation by the drug suramin.},
journal = {Scientific reports},
volume = {13},
number = {1},
issn = {2045-2322},
address = {[London]},
publisher = {Macmillan Publishers Limited, part of Springer Nature},
reportid = {DZNE-2023-00340},
pages = {3963},
year = {2023},
note = {CC BY},
abstract = {Tau is an intrinsically disordered neuronal protein in the
central nervous system. Aggregated Tau is the main component
of neurofibrillary tangles observed in Alzheimer's disease.
In vitro, Tau aggregation can be triggered by polyanionic
co-factors, like RNA or heparin. At different concentration
ratios, the same polyanions can induce Tau condensates via
liquid-liquid phase separation (LLPS), which over time
develop pathological aggregation seeding potential. Data
obtained by time resolved Dynamic Light Scattering
experiments (trDLS), light and electron microscopy show that
intermolecular electrostatic interactions between Tau and
the negatively charged drug suramin induce Tau condensation
and compete with the interactions driving and stabilizing
the formation of Tau:heparin and Tau:RNA coacervates, thus,
reducing their potential to induce cellular Tau aggregation.
Tau:suramin condensates do not seed Tau aggregation in a HEK
cell model for Tau aggregation, even after extended
incubation. These observations indicate that
electrostatically driven Tau condensation can occur without
pathological aggregation when initiated by small anionic
molecules. Our results provide a novel avenue for
therapeutic intervention of aberrant Tau phase separation,
utilizing small anionic compounds.},
keywords = {Humans / tau Proteins: metabolism / Suramin: pharmacology /
Alzheimer Disease: metabolism / Heparin / RNA: metabolism /
tau Proteins (NLM Chemicals) / Suramin (NLM Chemicals) /
Heparin (NLM Chemicals) / RNA (NLM Chemicals)},
cin = {AG Wegmann / AG Mandelkow 1},
ddc = {600},
cid = {I:(DE-2719)1810006 / I:(DE-2719)1013014},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36894559},
pmc = {pmc:PMC9997437},
doi = {10.1038/s41598-023-29846-9},
url = {https://pub.dzne.de/record/256516},
}