Fisetin for Parkinson's Disease
Also known as: 3,3',4',7-Tetrahydroxyflavone
Fisetin's senolytic and anti-inflammatory effects target both cellular senescence and neuroinflammation in Parkinson's disease.
Mechanism of Action
Fisetin clears senescent microglia and astrocytes that produce inflammatory SASP factors. It activates Nrf2 to restore antioxidant defense in dopaminergic neurons, inhibits α-synuclein aggregation, and promotes BDNF expression.
General mechanism: Bioactive flavonoid. Senolytic (PI3K/Akt/mTOR), Nrf2 activator, GSK3β inhibitor, anti-inflammatory, pro-apoptotic in cancer cells.
Current Evidence
Preclinical models show dopaminergic neuroprotection. Senolytic mechanism characterized in aged mice. No PD-specific clinical trials.
Clinical Status: Preclinical. Senolytic dosing from AFFIRM trial informs future PD studies.
Safety Profile
Very safe. Low oral bioavailability. Liposomal formulations being developed. No significant side effects.
Key Research Questions
- Can periodic fisetin senolytics slow PD progression?
- Does fisetin protect dopaminergic neurons through Nrf2 or senolytic mechanisms primarily?