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

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.

SUBMITTER: Ciccone L

PROVIDER: S-EPMC9921273 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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

Ciccone Lidia L Nencetti Susanna S Rossello Armando A Barlettani Lucia L Tonali Nicolò N Nieri Paola P Orlandini Elisabetta E

Nutrients 20230201 3

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 ...[more]

PMID: 36771455

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Project description:Dysregulation of neuropeptides may play an important role in aging-induced impairments. Among them, pituitary adenylate cyclase-activating polypeptide (PACAP) is a potent cytoprotective peptide that provides an endogenous control against a variety of tissue-damaging stimuli. We hypothesized that the progressive decline of PACAP throughout life and the well-known general cytoprotective effects of PACAP lead to age-related pathophysiological changes in PACAP deficiency, supported by the increased vulnerability to various stressors of animals partially or totally lacking PACAP. Using young and aging CD1 PACAP knockout (KO) and wild type (WT) mice, we demonstrated pre-senile amyloidosis in young PACAP KO animals and showed that senile amyloidosis appeared accelerated, more generalized, more severe, and affected more individuals. Histopathology showed age-related systemic amyloidosis with mainly kidney, spleen, liver, skin, thyroid, intestinal, tracheal, and esophageal involvement. Mass spectrometry-based proteomic analysis, reconfirmed with immunohistochemistry, revealed that apolipoprotein-AIV was the main amyloid protein in the deposits together with several accompanying proteins. Although the local amyloidogenic protein expression was disturbed in KO animals, no difference was found in laboratory lipid parameters, suggesting a complex pathway leading to increased age-related degeneration with amyloid deposits in the absence of PACAP. In spite of no marked inflammatory histological changes or blood test parameters, we detected a disturbed cytokine profile that possibly creates a pro-inflammatory milieu favoring amyloid deposition. In summary, here we describe accelerated systemic senile amyloidosis in PACAP gene-deficient mice, which might indicate an early aging phenomenon in this mouse strain. Thus, PACAP KO mice could serve as a model of accelerated aging with human relevance. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Dataset Information

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

Publications

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

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