Fucosterol from edible brown seaweeds has various biological activities, including anti-inflammatory, anti-adipogenic, antiphotoaging, anti-acetylcholinesterase, and anti-beta-secretase 1 activities.
This study was conducted to investigate the neuroprotective effects of fucosterol against sAβ1-42-induced ER stress and cognitive impairment in aging rats.
sAβ1-42decreased hippocampal neuronal viability by increasing GRP78 expression and intracellular calcium influx; these were attenuated by fucosterol pretreatment for 24 h prior to sAβ1-42 treatment.
In addition, sAβ1-42-induced ER stress was associated with the phosphorylation of JNK linked to the NMDA receptor, which was also reduced by fucosterol pretreatment via the activation of BDNF-TrkB-ERK1/2 signaling.
Furthermore, a single injection of sAβ1-42 into the dentate gyrus of the hippocampi of aging rats increased ER stress and decreased BDNF expression and spatial memory, which were alleviated by chronic fucosterol infusion.
These results showed that fucosterol decreased sAβ1-42-induced ER stress and cognitive dysfunction via the activation of BDNF-TrkB-ERK1/2 signaling, suggesting that ER stress-induced aging-associated cognitive dysfunction could be attenuated by fucosterol treatment.
Aging induces the dysregulation of proteostasis and the accumulation of sAβ1-42 that can lead to the modulation of synaptic activity and cognitive impairment.
Thus, a disturbance in proteostasis related to ER stress response is one of the major risk factors for neurodegenerative diseases, such as AD. Aging-induced impaired regulation of proteostasis is associated with perturbed calcium regulation that results in ER stress.
Calcium overload results in the dysregulation of protein phosphorylation, cytoskeletal dynamics, and gene expression, which adversely affect synaptic remodeling for memory consolidation.
These results indicated that fucosterol isolated from E. stolonifera enhanced the viability by reducing sAβ1-42-induced calcium overload in hippocampal neurons, suggesting that calcium-mediated ER stress could be regulated by fucosterol treatment.
However, little is known about its effects on soluble amyloid beta peptide (sAβ)-induced endoplasmic reticulum (ER) stress and cognitive impairment. Fucosterol was isolated from the edible brown seaweed Ecklonia stolonifera, and its neuroprotective effects were analyzed in primary hippocampal neurons and in aging rats.
Fucosterol attenuated sAβ1-42-induced decrease in the viability of hippocampal neurons and downregulated sAβ1-42-induced increase in glucose-regulated protein 78 (GRP78) expression in hippocampal neurons via activation of tyrosine receptor kinase B-mediated ERK1/2 signaling.
Fucosterol co-infusion attenuated sAβ1-42-induced cognitive impairment in aging rats via downregulation of GRP78 expression and upregulation of mature brain-derived neurotrophic factor expression in the dentate gyrus. Fucosterol might be beneficial for the management of cognitive dysfunction via suppression of aging-induced ER stress.