A peptide fraction of Olive Flounder (Paralichthys olivaceus) Skin Hydrolysate Inhibits Amyloid-β Generation in SH-SY5Y Cells via Suppression of BACE1 Expression

Abstract

The prevalence of degenerative neuro-diseases such as Alzheimer’s disease has increased with an increase in the life expectancy especially as seen in developed countries. According to the Amyloid Hypothesis, β-secretase leads to the onset of Alzheimer's disease though the generation of amyloid-β by proteolysis of amyloid precursor protein. Amyloid-β aggregates to form oligomers that build up to form plaques. Olive flounder (Paralichthys olivaceus) is high in protein content, with a higher protein content in skin (27.65%) compared to muscle (19.65%) according to proximate analysis results. Enzyme hydrolysates were prepared from skin and muscle using several enzymes. The neutrase skin hydrolysate showed the highest β-secretase inhibitory activity IC50 0.61 mg/mL. Purification steps were performed using ion exchange chromatography on QMA and CM-cellulose columns and SPE C18 column to produce an active fraction QMA-F1 with an IC50 value of 32.80 µg/mL. QMA-F1 was non-cytotoxic to SH-SY5Y cells, reduced BACE1 overexpression and attenuated amyloidogenesis. This suggests that the active β-secretase inhibitory peptides from olive flounder skin hydrolysates can be utilized as an ingredient in development of new pharmaceutical and nutraceutical therapeutic agents for Alzheimer’s Disease.