1. Secondary structure and toxicity of transthyretin fibrils can be altered by unsaturated fatty acids.
- Author
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Ali, Abid, Zhaliazka, Kiryl, Dou, Tianyi, Holman, Aidan P., Kumar, Rakesh, and Kurouski, Dmitry
- Subjects
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TRANSTHYRETIN , *PROTEIN transport , *FATTY acids , *CARRIER proteins , *AMYLOID beta-protein - Abstract
Transthyretin amyloidosis is a severe pathology characterized by the progressive accumulation of transthyretin (TTR) in various organs and tissues. This highly conserved through vertebrate evolution protein transports thyroid hormone thyroxine. In our bodies, TTR can interact with a large number of molecules, including ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) that are broadly used as food supplies. In this study, we investigated the effect of ω-3 and ω-6 PUFAs, as well as their fully saturated analog, on TTR aggregation. Our results showed that both ω-3 and ω-6 PUFAs strongly decreased the rate of TTR aggregation. We also found that in the presence of PUFAs, TTR formed morphologically different fibrils compared to the lipid-free environment. Nano-Infrared imaging revealed that these fibrils had drastically different secondary structures compared to the secondary structure of TTR aggregates formed in the PUFAs-free environment. Furthermore, TTR fibrils formed in the presence of ω-3 and ω-6 PUFAs exerted significantly lower cell toxicity compared to the fibrils formed in the absence of fatty acids. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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