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dGAE(297-391) Tau Fragment Promotes Formation of Chronic Traumatic Encephalopathy-Like Tau Filaments

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KITOKA Kristine LENDS Alons KUČINSKAS Gytis BULA Anna Lina KRASAUSKAS Lukas SMIRNOVAS Vytautas ZILKOVA Monika KOVACECH Branislav SKRABANA Rostislav HRITZ Jozef JAUDZEMS Kristaps

Rok publikování 2024
Druh Článek v odborném periodiku
Časopis / Zdroj Angewandte Chemie International Edition
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
www https://onlinelibrary.wiley.com/doi/10.1002/anie.202407821
Doi http://dx.doi.org/10.1002/anie.202407821
Klíčová slova tauopathies; tau protein; dGAE fragment; filamentous aggregates; NMR spectroscopy
Popis The microtubule-associated protein tau forms disease-specific filamentous aggregates in several different neurodegenerative diseases. In order to understand how tau undergoes misfolding into a specific filament type and to control this process for drug development purposes, it is crucial to study in vitro tau aggregation methods and investigate the structures of the obtained filaments at the atomic level. Here, we used the tau fragment dGAE, which aggregates spontaneously, to seed the formation of full-length tau filaments. The structures of dGAE and full-length tau filaments were investigated by magic-angle spinning (MAS) solid-state NMR, showing that dGAE allows propagation of a chronic traumatic encephalopathy (CTE)-like fold to the full-length tau. The obtained filaments efficiently seeded tau aggregation in HEK293T cells. This work demonstrates that in vitro preparation of disease-specific types of full-length tau filaments is feasible.
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