Neuroprotective Effect of β-secretase Inhibitory Peptide from Pacific Hake (Merluccius productus) Fish Protein Hydrolysate.
BACKGROUND
Various methodologies have been employed for the therapeutic interpolation of the progressive brain disorder Alzheimer's disease. Thus, β-secretase inhibition is significant to prevent disease progression in the early stages.


OBJECTIVE
This study seeks to purify and characterize a novel β-secretase inhibitory peptide from Pacific hake enzymatic hydrolysate.


METHODS
A potent β-secretase inhibitory peptide was isolated by sequential purifications using Sephadex G-25 column chromatography and octadecylsilane (ODS) C18 reversed-phase HPLC. A total of seven peptides were synthesized using the isolated peptide sequences. SH-SY5Y cells stably transfected with the human ''Swedish'' amyloid precursor protein (APP) mutation APP695 (SH-SY5YAPP695swe) were used as an in-vitro model system to investigate the effect of Leu-Asn peptide on APP processing.


RESULTS
The β-secretase inhibitory activity (IC50) of the purified peptide (Ser-Leu-Ala-Phe-Val-Asp- Asp-Val-Leu-Asn) from fish protein hydrolysate was 18.65 μM and dipeptide Leu-Asn was the most potent β-secretase inhibitor (IC50 value = 8.82 µM). When comparing all the seven peptides, the inhibition pattern of Leu-Asn dipeptide was found to be competitive by Lineweaver-Burk plot and Dixon plot (Ki value = 4.24 µM). The 24 h treatment with Leu-Asn peptide in SH-SY5Y cells resulted in reducing the β-amyloid (Aβ) production in a dose-dependent manner.


CONCLUSION
Therefore, the results of this study suggest that β-secretase inhibitory peptides derived from marine organisms could be potential candidates to develop nutraceuticals or pharmaceuticals as antidementia agents.
['Lee|Jung Kwon|JK|', 'Li-Chan|Eunice C Y|ECY|', 'Cheung|Imelda W Y|IWY|', 'Jeon|You-Jin|YJ|', 'Ko|Ju-Young|JY|', 'Byun|Hee-Guk|HG|']
D053829:Amyloid Precursor Protein Secretases D016564:Amyloid beta-Protein Precursor D000818:Animals D004791:Enzyme Inhibitors D029941:Fish Proteins D048388:Gadiformes D006801:Humans D018696:Neuroprotective Agents D010455:Peptides D011492:Protein Hydrolysates
peptide fish protein hydrolysate amyloid precursor protein β-amyloid Alzheimer's
disease β-secretase inhibitory activity.