Journal
MOLECULES
Volume 26, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/molecules26113353
Keywords
alpha-synuclein; dopamine transporter; flavonoid; Parkinson's Disease
Funding
- Fundacao para a Ciencia e Tecnologia (FCT)/Ministerio da Ciencia e do Ensino Superior [LISBOA-01-0145-FEDER-007344]
- FEDER under the PT2020 Partnership Agreement
- FCT [SFRH/BD/116597/2016]
- BacHBerry [FP7-613793]
- FCT Scientific Employment Stimulus Contract [CEEC/04567/CBIOS/2020]
- DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB)
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy [EXC 2067/1-390729940]
- European Research Council (ERC) under the European Union's Horizon 2020 Research and Innovation Programme [804229]
- European Research Council (ERC) [804229] Funding Source: European Research Council (ERC)
- Fundação para a Ciência e a Tecnologia [SFRH/BD/116597/2016] Funding Source: FCT
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The study found that fisetin has neuroprotective effects and modulates cellular pathologies related to Parkinson's Disease, reducing the formation of PD hallmark inclusions and increasing dopamine transporter levels.
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 alpha-synuclein (alpha syn)-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 asyn inclusions as well as their size and subcellular localization in a yeast model of asyn aggregation. Overall, our data show that fisetin exerts modulatory activities toward common cellular pathologies present in PD; remarkably, it modulates asyn aggregation, supporting the idea that diets rich in this compound may prove beneficial.
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