(Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasis

Abstract Parkinson’s disease (PD) is an age-related neurodegenerative disease associated with the misfolding and aggregation of alpha-synuclein (aSyn). The molecular underpinnings of PD are still obscure, but nutrition may play an important role in the prevention, onset, and disease progression. Die...

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Autores principales:	Diana Macedo, Carolina Jardim, Inês Figueira, A. Filipa Almeida, Gordon J. McDougall, Derek Stewart, Jose E. Yuste, Francisco A. Tomás-Barberán, Sandra Tenreiro, Tiago F. Outeiro, Cláudia N. Santos
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b63714c237644fb09216d02bf2765b49
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spelling	oai:doaj.org-article:b63714c237644fb09216d02bf2765b492021-12-02T15:09:03Z(Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasis10.1038/s41598-018-25118-z2045-2322https://doaj.org/article/b63714c237644fb09216d02bf2765b492018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25118-zhttps://doaj.org/toc/2045-2322Abstract Parkinson’s disease (PD) is an age-related neurodegenerative disease associated with the misfolding and aggregation of alpha-synuclein (aSyn). The molecular underpinnings of PD are still obscure, but nutrition may play an important role in the prevention, onset, and disease progression. Dietary (poly)phenols revert and prevent age-related cognitive decline and neurodegeneration in model systems. However, only limited attempts were made to evaluate the impact of digestion on the bioactivities of (poly)phenols and determine their mechanisms of action. This constitutes a challenge for the development of (poly)phenol-based nutritional therapies. Here, we subjected (poly)phenols from Arbutus unedo to in vitro digestion and tested the products in cell models of PD based on the cytotoxicity of aSyn. The (poly)phenol-digested metabolites from A. unedo leaves (LPDMs) effectively counteracted aSyn and H2O2 toxicity in yeast and human cells, improving viability by reducing aSyn aggregation and inducing its clearance. In addition, LPDMs modulated pathways associated with aSyn toxicity, such as oxidative stress, endoplasmic reticulum (ER) stress, mitochondrial impairment, and SIR2 expression. Overall, LPDMs reduced aSyn toxicity, enhanced the efficiency of ER-associated protein degradation by the proteasome and autophagy, and reduced oxidative stress. In total, our study opens novel avenues for the exploitation of (poly)phenols in nutrition and health.Diana MacedoCarolina JardimInês FigueiraA. Filipa AlmeidaGordon J. McDougallDerek StewartJose E. YusteFrancisco A. Tomás-BarberánSandra TenreiroTiago F. OuteiroCláudia N. SantosNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-15 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Diana Macedo Carolina Jardim Inês Figueira A. Filipa Almeida Gordon J. McDougall Derek Stewart Jose E. Yuste Francisco A. Tomás-Barberán Sandra Tenreiro Tiago F. Outeiro Cláudia N. Santos (Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasis
description	Abstract Parkinson’s disease (PD) is an age-related neurodegenerative disease associated with the misfolding and aggregation of alpha-synuclein (aSyn). The molecular underpinnings of PD are still obscure, but nutrition may play an important role in the prevention, onset, and disease progression. Dietary (poly)phenols revert and prevent age-related cognitive decline and neurodegeneration in model systems. However, only limited attempts were made to evaluate the impact of digestion on the bioactivities of (poly)phenols and determine their mechanisms of action. This constitutes a challenge for the development of (poly)phenol-based nutritional therapies. Here, we subjected (poly)phenols from Arbutus unedo to in vitro digestion and tested the products in cell models of PD based on the cytotoxicity of aSyn. The (poly)phenol-digested metabolites from A. unedo leaves (LPDMs) effectively counteracted aSyn and H2O2 toxicity in yeast and human cells, improving viability by reducing aSyn aggregation and inducing its clearance. In addition, LPDMs modulated pathways associated with aSyn toxicity, such as oxidative stress, endoplasmic reticulum (ER) stress, mitochondrial impairment, and SIR2 expression. Overall, LPDMs reduced aSyn toxicity, enhanced the efficiency of ER-associated protein degradation by the proteasome and autophagy, and reduced oxidative stress. In total, our study opens novel avenues for the exploitation of (poly)phenols in nutrition and health.
format	article
author	Diana Macedo Carolina Jardim Inês Figueira A. Filipa Almeida Gordon J. McDougall Derek Stewart Jose E. Yuste Francisco A. Tomás-Barberán Sandra Tenreiro Tiago F. Outeiro Cláudia N. Santos
author_facet	Diana Macedo Carolina Jardim Inês Figueira A. Filipa Almeida Gordon J. McDougall Derek Stewart Jose E. Yuste Francisco A. Tomás-Barberán Sandra Tenreiro Tiago F. Outeiro Cláudia N. Santos
author_sort	Diana Macedo
title	(Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasis
title_short	(Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasis
title_full	(Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasis
title_fullStr	(Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasis
title_full_unstemmed	(Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasis
title_sort	(poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasis
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/b63714c237644fb09216d02bf2765b49
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(Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasis

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