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. 2023 Feb 1;15(3):749.
doi: 10.3390/nu15030749.

Omega-3 PUFAs as a Dietary Supplement in Senile Systemic Amyloidosis

Lidia Ciccone  1 , Susanna Nencetti  1   2 , Armando Rossello  1   2   3 , Lucia Barlettani  1 , Nicolò Tonali  4 , Paola Nieri  1   2 , Elisabetta Orlandini  3   5
Affiliations

Omega-3 PUFAs as a Dietary Supplement in Senile Systemic Amyloidosis

Lidia Ciccone et al. Nutrients. .

Abstract

Eicosapentaenoic acid (EPA; 20:5) and docosahexaenoic acid (DHA; 22:6), two omega-3 poly-unsaturated fatty acids (PUFAs), are the main components in oil derived from fish and other marine organisms. EPA and DHA are commercially available as dietary supplements and are considered to be very safe and contribute to guaranteeing human health. Studies report that PUFAs have a role in contrasting neurodegenerative processes related to amyloidogenic proteins, such as β-amyloid for AD, α-synuclein in PD, and transthyretin (TTR) in TTR amyloidosis. In this context, we investigated if EPA and DHA can interact directly with TTR, binding inside the thyroxin-binding pockets (T4BP) that contribute to the tetramer stabilization. The data obtained showed that EPA and DHA can contribute to stabilizing the TTR tetramer through interactions with T4BP.

Keywords: DHA; EPA; TTR; amyloidosis; diet; fatty acids; fish oil; neuroprotection; omega 3; supplements.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) Chemical structures of EPA and DHA (B) Tetrameric structure of TTR (pdb structure 1sn0), two thyroxine molecules bind the TTR-binding sites. Structural figures were made by PyMOL using our scripts [13,14,15].
Figure 2
Figure 2
Graphic representation of the TTRs physiological and pathological roles in the body and in the CNS.
Figure 3
Figure 3
In vitro acid denaturation mediated of wt-TTR. The FF in absence of any inhibitor was assigned to be 100%. Results are shown as mean ± SEM. Statistical significance is calculated by one-way ANOVA test and Turkey post hoc test: * indicates significant difference vs. TTR (**** p < 0.0001, *** p < 0.001 and ** p < 0.01).
Figure 4
Figure 4
In vitro ThT fluorescence assay of wt-TTR in the absence or in the presence of diflunisal, DHA, and EPA. Values represent the fluorescence intensity mean ± SEM. The significance compared to TTR alone is assessed by one-way ANOVA test and Turkey post hoc test: * indicates significant difference vs. TTR (* p < 0.05).
Figure 5
Figure 5
The general profile of ANS displacement binding assay for studied compounds. (A) The TTR-ANS complex was titrated with different concentrations of EPA and (B) of DHA.
See this image and copyright information in PMC

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