title: (Poly)phenols protect from α-synuclein toxicity by reducing oxidative stress and promoting autophagy.
abstract: Parkinson's disease (PD) is the most common movement neurodegenerative disorder and is associated with the aggregation of α-synuclein (αSyn) and oxidative stress, hallmarks of the disease. Although the precise molecular events underlying αSyn aggregation are still unclear, oxidative stress is known to contribute to this process. Therefore, agents that either prevent oxidative stress or inhibit αSyn toxicity are expected to constitute potential drug leads for PD. Both pre-clinical and clinical studies provided evidence that (poly)phenols, pure or in extracts, might protect against neurodegenerative disorders associated with oxidative stress in the brain. In this study, we analyzed, for the first time, a (poly)phenol-enriched fraction (PEF) from leaves of Corema album, and used in vitro and cellular models to evaluate its effects on αSyn toxicity and aggregation. Interestingly, the PEF promoted the formation of non-toxic αSyn species in vitro, and inhibited its toxicity and aggregation in cells, by promoting the autophagic flux and reducing oxidative stress. Thus, C. album (poly)phenols appear as promising cytoprotective compounds, modulating central events in the pathogenesis of PD, such as αSyn aggregation and the impairment of autophagy. Ultimately, the understanding of the molecular effects of (poly)phenols will open novel opportunities for the exploitation of their beneficial effects and for drug development.
authors.affiliation: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Av. da República, Oeiras 2780-157, Portugal, Cell and Molecular Neuroscience Unit, Instituto de Medicina Molecular, Av. Prof. Egas Moniz, Lisboa 1649-028, Portugal.
authors.forename: Diana
authors.initials: D
authors.lastname: Macedo
authors.affiliation: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Av. da República, Oeiras 2780-157, Portugal.
authors.forename: Lucélia
authors.initials: L
authors.lastname: Tavares
authors.affiliation: Environmental and Biochemical Science Group, Enhancing Crop Productivity and Utilisation Theme, The James Hutton Institute, Dundee DD2 5DA, UK.
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: McDougall
authors.affiliation: Cell and Molecular Neuroscience Unit, Instituto de Medicina Molecular, Av. Prof. Egas Moniz, Lisboa 1649-028, Portugal.
authors.forename: Hugo
authors.initials: H
authors.lastname: Vicente Miranda
authors.affiliation: Environmental and Biochemical Science Group, Enhancing Crop Productivity and Utilisation Theme, The James Hutton Institute, Dundee DD2 5DA, UK, School of Life Sciences, Heriot-Watt University, Edinburgh EH14 4AS, UK.
authors.forename: Derek
authors.initials: D
authors.lastname: Stewart
authors.affiliation: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Av. da República, Oeiras 2780-157, Portugal, Departamento de Botânica e Engenharia Biológica, Instituto Superior de Agronomia, Universidade Técnica de Lisboa, Tapada da Ajuda, Lisboa 1349-017, Portugal.
authors.forename: Ricardo B
authors.initials: RB
authors.lastname: Ferreira
authors.affiliation: Cell and Molecular Neuroscience Unit, Instituto de Medicina Molecular, Av. Prof. Egas Moniz, Lisboa 1649-028, Portugal, stenreiro@gmail.com touteiro@gmail.com csantos@itqb.unl.pt.
authors.forename: Sandra
authors.initials: S
authors.lastname: Tenreiro
authors.affiliation: Cell and Molecular Neuroscience Unit, Instituto de Medicina Molecular, Av. Prof. Egas Moniz, Lisboa 1649-028, Portugal, Instituto de Fisiologia, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, Lisboa 1649-028, Portugal Department of Neurodegeneration and Restorative Research, Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University Medical Center Göttingen, Waldweg 33, Göttingen 37073, Germany stenreiro@gmail.com touteiro@gmail.com csantos@itqb.unl.pt.
authors.forename: Tiago F
authors.initials: TF
authors.lastname: Outeiro
authors.affiliation: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Av. da República, Oeiras 2780-157, Portugal, Instituto de Biologia Experimental e Tecnológica, Apartado 12, Oeiras 2781-901, Portugal, stenreiro@gmail.com touteiro@gmail.com csantos@itqb.unl.pt.
authors.forename: Cláudia N
authors.initials: CN
authors.lastname: Santos
mesh_terms: D000978:Antiparkinson Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D010300:Parkinson Disease / Q000188:drug therapy; D059808:Polyphenols / Q000494:pharmacology*; D051844:alpha-Synuclein / Q000633:toxicity*
chemical_list: D000978:Antiparkinson Agents; D059808:Polyphenols; D051844:alpha-Synuclein