Jung Kwon Lee, Eunice C.Y. Li-Chan, Imelda W.Y. Cheung, You-Jin Jeon, Ju-Young Ko and Hee-Guk Byun* Pages 1028 - 1038 ( 11 )
<P>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. </P><P> Objective: This study seeks to purify and characterize a novel β-secretase inhibitory peptide from Pacific hake enzymatic hydrolysate. </P><P> 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. </P><P> 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. </P><P> 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.</P>
β-secretase inhibitory activity, fish protein hydrolysate, peptide, β-amyloid, amyloid precursor protein, Alzheimer's disease.
Department of Marine Biotechnology, Gangneung-Wonju National University, Gangneung 25457, Food, Nutrition & Health Program, Faculty of Land & Food Systems, The University of British Columbia, 2205 East Mall, Vancouver, BC, V6T 1Z4, Food, Nutrition & Health Program, Faculty of Land & Food Systems, The University of British Columbia, 2205 East Mall, Vancouver, BC, V6T 1Z4, Department of Marine Life Science, Jeju National University, Jeju 63243, Department of Marine Life Science, Jeju National University, Jeju 63243, Department of Marine Biotechnology, Gangneung-Wonju National University, Gangneung 25457