Abstract
Fucosterol from edible brown seaweeds has various biological activities, including anti-inflammatory, anti-adipogenic, antiphotoaging, anti-acetylcholinesterase, and anti-beta-secretase 1 activities. 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.
Highlights
The endoplasmic reticulum (ER), a key component of the proteostasis network, is an important organelle that plays a critical role in the correct synthesis, folding, and modification of proteins, as well as in intracellular calcium homeostasis [1,2]
Since fucosterol pretreatment attenuated sAβ1-42 -induced decrease in hippocampal neuronal viability, we further investigated the role of fucosterol in altering intracellular calcium levels involved in ER stress
This study was conducted to investigate the neuroprotective effects of fucosterol against sAβ1-42 -induced ER stress and cognitive impairment in aging rats. sAβ1-42 decreased hippocampal neuronal viability by increasing glucose-regulated protein 78 (GRP78) expression and intracellular calcium influx; these were attenuated by fucosterol pretreatment for 24 h prior to sAβ1-42 treatment
Summary
The endoplasmic reticulum (ER), a key component of the proteostasis network, is an important organelle that plays a critical role in the correct synthesis, folding, and modification of proteins, as well as in intracellular calcium homeostasis [1,2]. Recent studies have suggested that soluble Aβ (sAβ) induces loss of proteostasis and triggers synaptic dysfunction, inhibition of long-term potentiation, and disruption of memory in AD [7,8,9,10,11] These results suggest that age-induced cognitive impairment results from the dysregulation of proteostasis owing to exaggerated ER stress [12,13]. We hypothesized that fucosterol from Ecklonia stolonifera (E. stolonifera) could regulate sAβ1-42 -induced cognitive impairment via BDNF-mediated suppression of ER stress in the dorsal hippocampus of aging rats. To verify this hypothesis, first, we determined whether fucosterol could regulate sAβ1-42 -induced calcium dysregulation and ER stress in the primary hippocampal culture system. Using an in vivo behavioral study, we studied if fucosterol infusion attenuated sAβ1-42 -induced memory dysfunction in the dentate gyrus of the dorsal hippocampus in aging rats
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