dGAE(297–391) Tau Fragment Promotes Formation of Chronic Traumatic Encephalopathy‐Like Tau Filaments
Abstract 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.
Authors
- Vytautas Smirnovas (ORCID: https://orcid.org/0000-0002-1829-5455)
- Rostislav Škrabana (ORCID: https://orcid.org/0000-0001-8200-5275)
- Jozef Hritz (ORCID: https://orcid.org/0000-0002-4512-9241)
- Branislav Kováčech (ORCID: https://orcid.org/0000-0001-9383-2911)
- Alons Lends (ORCID: https://orcid.org/0000-0001-7883-613X)
- Monika Žilková (ORCID: https://orcid.org/0000-0002-5978-1695)
- Lukas Krasauskas (ORCID: https://orcid.org/0000-0001-9116-6599)
- Kristīne Kitoka (ORCID: https://orcid.org/0000-0003-2547-3675)
- Anna L. Bula (ORCID: https://orcid.org/0000-0003-4389-4131)
- Gytis Kučinskas
- Kristaps Jaudzems (ORCID: https://orcid.org/0000-0003-3922-2447)
Institutions
- Central European Institute of Technology (CZ)
- Institute of Chemistry of the Slovak Academy of Sciences (SK)
- Vilnius University (LT)
- Slovak Academy of Sciences (SK)
- Masaryk University (CZ)
- Central European Institute of Technology – Masaryk University (CZ)
- Latvijas Organiskās Sintēzes Institūts (LV)
- Institute of Neuroimmunology of the Slovak Academy of Sciences (SK)
- University of Latvia (LV)
Publication Details
- Journal
- Angewandte Chemie
- Published
- 2024-08-26
- DOI
- https://doi.org/10.1002/ange.202407821
- Citations
- 1
- Primary Topic
- Neuroscience and Neuropharmacology Research
- Type
- article
- Field-Weighted Citation Impact
- 0.27
Funders
- European Commission
- Ministerstvo Školství, Mládeže a Tělovýchovy
- Grantová Agentura České Republiky
- Agentúra na Podporu Výskumu a Vývoja
- Latvijas Zinātnes Padome
- Latvijas Universitate
- Vedecká Grantová Agentúra MŠVVaŠ SR a SAV
- Central European Institute of Technology
- Latvijas Universitātes Fonds
- HORIZON EUROPE Framework Programme
- European Regional Development Fund
- H2020 Marie Skłodowska-Curie Actions