Small Molecule Fisetin Modulates Alpha–Synuclein Aggregation
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 th...
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doaj-988f573f8bb3427e8cf7f560360726842021-06-30T23:07:16ZengMDPI AGMolecules1420-30492021-06-01263353335310.3390/molecules26113353Small Molecule Fisetin Modulates Alpha–Synuclein AggregationRita Rosado-Ramos0Joana Godinho-Pereira1Daniela Marques2Inês Figueira3Tiago Fleming Outeiro4Regina Menezes5Cláudia Nunes dos Santos6iBET, Instituto de Biologia Experimental e Tecnológica, Av. da República, Apartado 12, 2781-901 Oeiras, PortugaliBET, Instituto de Biologia Experimental e Tecnológica, Av. da República, Apartado 12, 2781-901 Oeiras, PortugalCEDOC, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, PortugaliBET, Instituto de Biologia Experimental e Tecnológica, Av. da República, Apartado 12, 2781-901 Oeiras, PortugalDepartment of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, 37073 Göttingen, GermanyiBET, Instituto de Biologia Experimental e Tecnológica, Av. da República, Apartado 12, 2781-901 Oeiras, PortugaliBET, Instituto de Biologia Experimental e Tecnológica, Av. da República, Apartado 12, 2781-901 Oeiras, PortugalPhenolic 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 <i>tert</i>-butyl hydroperoxide (<i>t</i>-BHP) and against methyl-4-phenylpyridinuim (MPP<sup>+</sup>)-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.https://www.mdpi.com/1420-3049/26/11/3353α-synucleindopamine transporterflavonoidParkinson’s Disease |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rita Rosado-Ramos Joana Godinho-Pereira Daniela Marques Inês Figueira Tiago Fleming Outeiro Regina Menezes Cláudia Nunes dos Santos |
spellingShingle |
Rita Rosado-Ramos Joana Godinho-Pereira Daniela Marques Inês Figueira Tiago Fleming Outeiro Regina Menezes Cláudia Nunes dos Santos Small Molecule Fisetin Modulates Alpha–Synuclein Aggregation Molecules α-synuclein dopamine transporter flavonoid Parkinson’s Disease |
author_facet |
Rita Rosado-Ramos Joana Godinho-Pereira Daniela Marques Inês Figueira Tiago Fleming Outeiro Regina Menezes Cláudia Nunes dos Santos |
author_sort |
Rita Rosado-Ramos |
title |
Small Molecule Fisetin Modulates Alpha–Synuclein Aggregation |
title_short |
Small Molecule Fisetin Modulates Alpha–Synuclein Aggregation |
title_full |
Small Molecule Fisetin Modulates Alpha–Synuclein Aggregation |
title_fullStr |
Small Molecule Fisetin Modulates Alpha–Synuclein Aggregation |
title_full_unstemmed |
Small Molecule Fisetin Modulates Alpha–Synuclein Aggregation |
title_sort |
small molecule fisetin modulates alpha–synuclein aggregation |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2021-06-01 |
description |
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 <i>tert</i>-butyl hydroperoxide (<i>t</i>-BHP) and against methyl-4-phenylpyridinuim (MPP<sup>+</sup>)-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. |
topic |
α-synuclein dopamine transporter flavonoid Parkinson’s Disease |
url |
https://www.mdpi.com/1420-3049/26/11/3353 |
work_keys_str_mv |
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