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.

Details

Title
(Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasis
Author
Macedo, Diana 1   VIAFID ORCID Logo  ; Jardim, Carolina 2 ; Figueira, Inês 2 ; Almeida, A Filipa 2   VIAFID ORCID Logo  ; McDougall, Gordon J 3   VIAFID ORCID Logo  ; Stewart, Derek 4 ; Yuste, Jose E 5 ; Tomás-Barberán, Francisco A 5   VIAFID ORCID Logo  ; Tenreiro, Sandra 6 ; Outeiro, Tiago F 7   VIAFID ORCID Logo  ; Santos, Cláudia N 2   VIAFID ORCID Logo 

 Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, Oeiras, Portugal; iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, Oeiras, Portugal; Instituto de Medicina Molecular João Lobo Antunes, Avenida Professor Egas Moniz, Lisboa, Portugal 
 Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, Oeiras, Portugal; iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, Oeiras, Portugal 
 Environmental and Biochemical Science Group, The James Hutton Institute, Dundee, Scotland, UK 
 Environmental and Biochemical Science Group, The James Hutton Institute, Dundee, Scotland, UK; School of of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh, UK 
 Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 30100 Campus de Espinardo, Murcia, Spain 
 CEDOC – Chronic Diseases Research Center, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal 
 CEDOC – Chronic Diseases Research Center, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal; Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University Medical Center Göttingen, Waldweg 33, Göttingen, Germany; Max Planck Institute for Experimental Medicine, Göttingen, Germany 
Pages
1-15
Publication year
2018
Publication date
May 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2034275166
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.