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Related Experiment Video

Updated: Oct 31, 2025

Exogenous Administration of Microsomes-associated Alpha-synuclein Aggregates to Primary Neurons As a Powerful Cell Model of Fibrils Formation
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Small Molecule Fisetin Modulates Alpha-Synuclein Aggregation.

Rita Rosado-Ramos1,2,3, Joana Godinho-Pereira1,2, Daniela Marques3

  • 1iBET, Instituto de Biologia Experimental e Tecnológica, Av. da República, Apartado 12, 2781-901 Oeiras, Portugal.

Molecules (Basel, Switzerland)
|July 2, 2021
PubMed
Summary

Fisetin, a dietary flavonoid, shows neuroprotective effects against Parkinson's Disease (PD) hallmarks. It reduces oxidative stress, dopaminergic neuron toxicity, and alpha-synuclein aggregation, suggesting dietary fisetin may benefit PD prevention.

Keywords:
Parkinson’s Diseasedopamine transporterflavonoidα-synuclein

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Pharmacology

Background:

  • Neurodegenerative diseases (ND), including Parkinson's Disease (PD), are characterized by motor deficits, alpha-synuclein (αsyn) aggregation, oxidative stress, and neuroinflammation.
  • Dietary phenolic compounds are investigated for their potential role in preventing ND.

Purpose of the Study:

  • To evaluate the neuroprotective activity of fisetin, a dietary flavonoid, against key pathological features of Parkinson's Disease (PD) using cellular models.
  • To determine fisetin's effects on oxidative stress, dopaminergic neuron toxicity, and αsyn aggregation.

Main Methods:

  • SH-SY5Y and Lund human Mesencephalic (LUHMES) cells were used to model PD-related cellular pathologies.
  • Cells were exposed to oxidative stress (tert-butyl hydroperoxide) and neurotoxicity (MPP+) with and without fisetin treatment.
  • A yeast model was employed to assess fisetin's impact on αsyn aggregation.

Main Results:

  • Fisetin demonstrated protective effects against oxidative stress and MPP+-induced toxicity in dopaminergic neurons at physiologically relevant concentrations.
  • Fisetin treatment increased dopamine transporter levels in LUHMES cells.
  • Fisetin significantly reduced the percentage, size, and altered subcellular localization of αsyn inclusions in the yeast model.

Conclusions:

  • Fisetin exhibits modulatory effects on cellular pathologies associated with PD, including oxidative stress and neuroinflammation.
  • Fisetin's ability to modulate αsyn aggregation is a significant finding, supporting its potential therapeutic role.
  • These findings suggest that a diet rich in fisetin may offer benefits for preventing or managing Parkinson's Disease.