NDLI: Small Molecule Fisetin Modulates Alpha–Synuclein Aggregation

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Small Molecule Fisetin Modulates Alpha–Synuclein Aggregation

Content Provider	MDPI
Author	Rosado-Ramos, Rita Godinho-Pereira, Joana Marques, Daniela Figueira, Inês Outeiro, Tiago Fleming Menezes, Regina Santos, Cláudia Nunes dos
Copyright Year	2021
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 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.
Starting Page	3353
e-ISSN	14203049
DOI	10.3390/molecules26113353
Journal	Molecules
Issue Number	11
Volume Number	26
Language	English
Publisher	MDPI
Publisher Date	2021-06-02
Access Restriction	Open
Subject Keyword	Molecules Toxicology Α-synuclein Dopamine Transporter Flavonoid Parkinson's Disease
Content Type	Text
Resource Type	Article

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