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Small molecule fisetin modulates alpha-Synuclein aggregation

Lookup NU author(s): Professor Tiago OuteiroORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 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.

Publication metadata

Author(s): Rosado-Ramos R, Godinho-Pereira J, Marques D, Figueira I, Outeiro TF, Menezes R, Dos Santos CN

Publication type: Article

Publication status: Published

Journal: Molecules

Year: 2021

Volume: 26

Issue: 11

Print publication date: 01/06/2021

Online publication date: 02/06/2021

Acceptance date: 27/05/2021

Date deposited: 28/06/2021

ISSN (electronic): 1420-3049

Publisher: MDPI AG


DOI: 10.3390/molecules26113353


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