(Poly)phenols protect from alpha-synuclein toxicity by reducing oxidative stress and promoting autophagy

Diana Macedo, Lucelia Tavares, Gordon J. McDougall, Hugo Vicente Miranda, Derek Stewart, Ricardo B. Ferreira, Sandra Tenreiro, Tiago F. Outeiro, Claudia N. Santos

    Research output: Contribution to journalArticle

    39 Citations (Scopus)

    Abstract

    Parkinson's disease (PD) is the most common movement neurodegenerative disorder and is associated with the aggregation of alpha-synuclein (alpha Syn) and oxidative stress, hallmarks of the disease. Although the precise molecular events underlying alpha Syn aggregation are still unclear, oxidative stress is known to contribute to this process. Therefore, agents that either prevent oxidative stress or inhibit alpha Syn 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 alpha Syn toxicity and aggregation. Interestingly, the PEF promoted the formation of non-toxic alpha Syn 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 alpha Syn 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.

    Original languageEnglish
    Pages (from-to)1717-1732
    Number of pages16
    JournalHuman Molecular Genetics
    Volume24
    Issue number6
    Early online date28 Nov 2014
    DOIs
    Publication statusPublished - 15 Mar 2015

    Keywords

    • CHAPERONE-MEDIATED AUTOPHAGY
    • PARKINSONS-DISEASE
    • PROTEASOMAL FUNCTION
    • ARBUTUS-UNEDO
    • YEAST-CELLS
    • POSTTRANSLATIONAL MODIFICATIONS
    • SACCHAROMYCES-CEREVISIAE
    • ANTIOXIDANT PROPERTIES
    • ALZHEIMERS-DISEASE
    • GINKGO-BILOBA

    Cite this

    Macedo, D., Tavares, L., McDougall, G. J., Miranda, H. V., Stewart, D., Ferreira, R. B., Tenreiro, S., Outeiro, T. F., & Santos, C. N. (2015). (Poly)phenols protect from alpha-synuclein toxicity by reducing oxidative stress and promoting autophagy. Human Molecular Genetics, 24(6), 1717-1732. https://doi.org/10.1093/hmg/ddu585