A novel BACE inhibitor isolated from Eisenia bicyclis exhibits neuroprotective activity against β-amyloid toxicity

Abstract Alzheimer’s disease (AD) is a disturbing and advanced neurodegenerative disease and is characterized pathologically by the accumulation of amyloid beta (Aβ) and the hyperphosphorylation of tau proteins in the brain. The deposition of Aβ aggregates triggers synaptic dysfunction, and neurodegeneration, which lead to cognitive disorders. Here, we found that FF isolated from an eatable perennial brown seaweed E.bicyclis protect against Aβ-induced neurotoxicity in neuroblastoma cells stably transfected with two amyloid precursor protein (APP) constructs: the APP695 cDNA (SH-SY5Y-APP695swe). The FF demonstrated strong inhibitory activity for β-secretase (IC50 16.1 μM) and its inhibition pattern was investigated using Lineweaver-Burk and Dixon plots, and found to be non-competitive. Then, we tested whether FF could inhibit production of Aβ in SH-SY5Y-APP695swe. FF inhibited the production of Aβ and soluble-APP, residue of APP from cleaved APP by β-secretase. Our data show that FF can inhibit the production of Aβ and soluble-APPβ via inhibition of β-secretase activity. Taken together these results suggest that FF may be worthy of future study as an anti-AD treatment.