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Current Alzheimer Research


ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Research Article

Neuroprotective Effect of β-secretase Inhibitory Peptide from Pacific Hake (Merluccius productus) Fish Protein Hydrolysate

Author(s): Jung Kwon Lee, Eunice C.Y. Li-Chan, Imelda W.Y. Cheung, You-Jin Jeon, Ju-Young Ko and Hee-Guk Byun*

Volume 16, Issue 11, 2019

Page: [1028 - 1038] Pages: 11

DOI: 10.2174/1567205016666191113122046

Price: $65


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.

Keywords: β-secretase inhibitory activity, fish protein hydrolysate, peptide, β-amyloid, amyloid precursor protein, Alzheimer's disease.

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