FUCOXANTHIN ENHANCES AUTOPHAGIC FLUX AND FERROPTOSIS-RELATED ANTIOXIDANT DEFENSE IN AN ALZHEIMER'S DISEASE MODEL

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) accumulation, autophagy dysfunction, and ferroptosis-related oxidative damage, ultimately leading to neuronal apoptosis. Impaired autophagy exacerbates Aβ deposition, while ferroptosis contributes to neurodegeneration through lipid peroxidation. Fucoxanthin, a marine carotenoid with neuroprotective properties, was investigated for its autophagy-modulating effects in SweAPP N2a cells, an amyloidogenic AD model. Fucoxanthin at 1 μM significantly upregulated LC3-II (p<0.01), ATG5 (p<0.001), and VPS34 (p<0.001), while downregulating p62 (p<0.05), indicating enhanced autophagic flux. It also selectively enhanced lysosomal function by increasing LAMP1 (1.4-fold) and Cathepsin D (2-fold), whereas LAMP2 expression remained unchanged. Furthermore, fucoxanthin activated autophagy via AMPK/mTOR/ULK signaling, increasing p-AMPK and ULK1 while significantly reducing p-mTOR. Fucoxanthin (5 μM) upregulated ferroptosis-related antioxidant defense markers, increasing GPX4 to 214% and FTH1 to 141% relative to the control (100%), suggesting protection against lipid peroxidation. Mechanistic studies showed that autophagy inhibition with 3-methyladenine attenuated fucoxanthin-induced autophagy activation, whereas co-treatment with rapamycin further enhanced autophagy-related responses. These findings suggest that fucoxanthin activates AMPK/mTOR/ULK1 signaling, restoring autophagic clearance of misfolded proteins and mitigating Aβ toxicity. By simultaneously promoting autophagy and ferroptosis-related antioxidant mechanisms, fucoxanthin represents a dual-targeting preventive strategy against AD pathology. This study highlights fucoxanthin’s potential as a neuroprotective compound supporting autophagy enhancement and oxidative stress defense, reinforcing its role in AD prevention.양식의 맨 위양식의 맨 아래