Author(s):
Rosado-Ramos, Rita ; Godinho-Pereira, Joana ; Marques, Daniela ; Figueira, Inês ; Outeiro, Tiago Fleming ; Menezes, Regina ; Dos Santos, Cláudia Nunes
Date: 2021
Persistent ID: http://hdl.handle.net/10362/126500
Origin: Repositório Institucional da UNL
Subject(s): Dopamine transporter; Flavonoid; Parkinson’s Disease; α-synuclein; Analytical Chemistry; Chemistry (miscellaneous); Molecular Medicine; Pharmaceutical Science; Drug Discovery; Physical and Theoretical Chemistry; Organic Chemistry; SDG 3 - Good Health and Well-being
Description
Funding Information: iNOVA4Health Research Unit (LISBOA-01-0145-FEDER-007344), which is co-funded by Funda??o para a Ci?ncia e Tecnologia (FCT)/Minist?rio da Ci?ncia e do Ensino Superior, through national funds, and by FEDER under the PT2020 Partnership Agreement, is acknowledged. Authors would like to acknowledge FCT for financial support of RR (SFRH/BD/116597/2016). JP, RR, GG, and CNS acknowledges funding via BacHBerry (Project No. FP7-613793; www.bachberry.eu). RM is funded by FCT Scientific Employment Stimulus Contract CEEC/04567/CBIOS/2020. TFO was supported by the DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB) and is currently supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany?s Excellence Strategy?EXC 2067/1-390729940. It is also acknowledged the European Research Council (ERC) under the European Union?s Horizon 2020 Research and Innovation Programme under Grant Agreement No. 804229. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Phenolic compounds are thought to be important to prevent neurodegenerative diseases (ND). Parkinson’s Disease (PD) is a neurodegenerative disorder known for its typical motor features, the deposition of α-synuclein (αsyn)-positive inclusions in the brain, and for concomitant cellular pathologies that include oxidative stress and neuroinflammation. Neuroprotective activity of fisetin, a dietary flavonoid, was evaluated against main hallmarks of PD in relevant cellular models. At physiologically relevant concentrations, fisetin protected SH-SY5Y cells against oxidative stress overtaken by tert-butyl hydroperoxide (t-BHP) and against methyl-4-phenylpyridinuim (MPP+)-induced toxicity in dopaminergic neurons, the differentiated Lund human Mesencephalic (LUHMES) cells. In this cellular model, fisetin promotes the increase of the levels of dopamine transporter. Remarkably, fisetin reduced the percentage of cells containing αsyn inclusions as well as their size and subcellular localization in a yeast model of αsyn aggregation. Overall, our data show that fisetin exerts modulatory activities toward common cellular pathologies present in PD; remarkably, it modulates αsyn aggregation, supporting the idea that diets rich in this compound may prove beneficial.
