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Title (Primary) Tau oligomers impair artificial membrane integrity and cellular viability
Author Flach, K.; Hilbrich, I.; Schiffmann, A.; Gärtner, U.; Krüger, M.; Leonhardt, M.; Waschipky, H.; Wick, L.; Arendt, T.; Holzer, M.;
Journal Journal of Biological Chemistry
Year 2012
Department UMB;
Volume 287
Issue 52
Language englisch;
Abstract

The microtubule-associated protein Tau is mainly expressed in neurons, where it binds and stabilizes microtubules. In Alzheimer disease and other tauopathies, Tau protein has a reduced affinity toward microtubules. As a consequence, Tau protein detaches from microtubules and eventually aggregates into β-sheet-containing filaments. The fibrillization of monomeric Tau to filaments is a multistep process that involves the formation of various aggregates, including spherical and protofibrillar oligomers. Previous concepts, primarily developed for Aβ and α-synuclein, propose these oligomeric intermediates as the primary cytotoxic species mediating their deleterious effects through membrane permeabilization. In the present study, we thus analyzed whether this concept can also be applied to Tau protein. To this end, viability and membrane integrity were assessed on SH-SY5Y neuroblastoma cells and artificial phospholipid vesicles, treated with Tau monomers, Tau aggregation intermediates, or Tau fibrils. Our findings suggest that oligomeric Tau aggregation intermediates are the most toxic compounds of Tau fibrillogenesis, which effectively decrease cell viability and increase phospholipid vesicle leakage. Our data integrate Tau protein into the class of amyloidogenic proteins and enforce the hypothesis of a common toxicity-mediating mechanism for amyloidogenic proteins.

ID 13261
Persistent UFZ Identifier https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=13261
Flach, K., Hilbrich, I., Schiffmann, A., Gärtner, U., Krüger, M., Leonhardt, M., Waschipky, H., Wick, L., Arendt, T., Holzer, M. (2012):
Tau oligomers impair artificial membrane integrity and cellular viability
J. Biol. Chem. 287 (52), 43223 - 43233