Fucoxanthin, a Marine Carotenoid, Attenuates β ‐Amyloid Oligomer‐Induced Neurotoxicity Possibly via Regulating the PI3K/Akt and the ERK Pathways in SH‐SY5Y Cells

Alzheimer’s disease (AD), the most common neurodegenerative disorder, is characterized by neurofibrillary tangles, synaptic impairments, and loss of neurons. Oligomers of β ‐amyloid (A β ) are widely accepted as the main neurotoxins to induce oxidative stress and neuronal loss in AD. In this study, we discovered that fucoxanthin, a marine carotenoid with antioxidative stress properties, concentration dependently prevented A β oligomer‐induced increase of neuronal apoptosis and intracellular reactive oxygen species in SH‐SY5Y cells. A β oligomers inhibited the prosurvival phosphoinositide 3‐kinase (PI3K)/Akt cascade and activated the proapoptotic extracellular signal‐regulated kinase (ERK) pathway. Moreover, inhibitors of glycogen synthase kinase 3 β (GSK3 β ) and mitogen‐activated protein kinase (MEK) synergistically prevented A β oligomer‐induced neuronal death, suggesting that the PI3K/Akt and ERK pathways might be involved in A β oligomer‐induced neurotoxicity. Pretreatment with fucoxanthin significantly prevented A β oligomer‐induced alteration of the PI3K/Akt and ERK pathways. Furthermore, LY294002 and wortmannin, two PI3K inhibitors, abolished the neuroprotective effects of fucoxanthin against A β oligomer‐induced neurotoxicity. These results suggested that fucoxanthin might prevent A β oligomer‐induced neuronal loss and oxidative stress via the activation of the PI3K/Akt cascade as well as inhibition of the ERK pathway, indicating that further studies of fucoxanthin and related compounds might lead to a useful treatment of AD.