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000256516 037__ $$aDZNE-2023-00340
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000256516 1001_ $$aPrince, Prabhu Rajaiah$$b0
000256516 245__ $$aInitiation and modulation of Tau protein phase separation by the drug suramin.
000256516 260__ $$a[London]$$bMacmillan Publishers Limited, part of Springer Nature$$c2023
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000256516 520__ $$aTau 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.
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000256516 650_7 $$2NLM Chemicals$$atau Proteins
000256516 650_7 $$06032D45BEM$$2NLM Chemicals$$aSuramin
000256516 650_7 $$09005-49-6$$2NLM Chemicals$$aHeparin
000256516 650_7 $$063231-63-0$$2NLM Chemicals$$aRNA
000256516 650_2 $$2MeSH$$aHumans
000256516 650_2 $$2MeSH$$atau Proteins: metabolism
000256516 650_2 $$2MeSH$$aSuramin: pharmacology
000256516 650_2 $$2MeSH$$aAlzheimer Disease: metabolism
000256516 650_2 $$2MeSH$$aHeparin
000256516 650_2 $$2MeSH$$aRNA: metabolism
000256516 7001_ $$0P:(DE-2719)2812812$$aHochmair, Janine$$b1$$eFirst author$$udzne
000256516 7001_ $$aBrognaro, Hévila$$b2
000256516 7001_ $$aGevorgyan, Susanna$$b3
000256516 7001_ $$0P:(DE-2719)9000550$$aFranck, Maximilian$$b4$$udzne
000256516 7001_ $$aSchubert, Robin$$b5
000256516 7001_ $$aLorenzen, Kristina$$b6
000256516 7001_ $$aYazici, Selin$$b7
000256516 7001_ $$0P:(DE-2719)2541671$$aMandelkow, Eckhard$$b8$$udzne
000256516 7001_ $$0P:(DE-2719)2812695$$aWegmann, Susanne$$b9$$udzne
000256516 7001_ $$aBetzel, Christian$$b10
000256516 773__ $$0PERI:(DE-600)2615211-3$$a10.1038/s41598-023-29846-9$$gVol. 13, no. 1, p. 3963$$n1$$p3963$$tScientific reports$$v13$$x2045-2322$$y2023
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