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dGAE(297-391) Tau Fragment Promotes Formation of Chronic Traumatic Encephalopathy-Like Tau Filaments
Kristine Kitoka1, Alons Lends1, Gytis Kucinskas2,3
1Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga LV, 1006, Latvia.
Angewandte Chemie (International Ed. in English)
|August 26, 2024
Summary
Researchers developed an in vitro method to create disease-specific tau filaments, crucial for understanding neurodegenerative diseases like chronic traumatic encephalopathy (CTE) and for drug development.
Area of Science:
- Neuroscience
- Biochemistry
- Structural Biology
Background:
- The microtubule-associated protein tau aggregates into disease-specific filaments in neurodegenerative conditions.
- Understanding tau misfolding and filament structures is key for developing therapeutic strategies.
Purpose of the Study:
- To establish an in vitro method for generating disease-specific full-length tau filaments.
- To investigate the atomic-level structures of tau filaments using a tau fragment (dGAE).
Main Methods:
- Utilized the dGAE tau fragment to seed the aggregation of full-length tau in vitro.
- Employed magic-angle spinning (MAS) solid-state NMR to determine filament structures.
- Assessed the seeding potential of in vitro-formed filaments in HEK293T cells.
Main Results:
- The dGAE fragment successfully induced the formation of full-length tau filaments.
- Demonstrated that dGAE promotes a chronic traumatic encephalopathy (CTE)-like fold in full-length tau.
- The generated tau filaments were potent inducers of tau aggregation in cellular models.
Conclusions:
- In vitro preparation of disease-specific full-length tau filaments is achievable.
- This method provides a platform for studying tauopathies and for drug discovery efforts.
- The findings offer insights into the structural basis of tau aggregation in CTE.
