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, Hee-Guk Byun*.

Journal Name: Current Alzheimer Research

Volume 16 , Issue 11 , 2019

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Abstract:

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.

[1]
Alzheimer A. Uber eine eigenartige Erkrankung der Hirnrinde. Allg Zeitschr f Psychiatr u Psych-Gerichtl Med (1907).
[2]
Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA. Alzheimer disease in the US population: Prevalence estimates using the 2000 census. Arch Neurol 60(8): 1119-22.(2003);
[3]
Joachim CL, Selkoe DJ. The seminal role of β-amyloid in the pathogenesis of Alzheimer disease. Alzheimer Dis Assoc Disord 6(1): 7-34.(1992);
[4]
Selkoe DJ. Alzheimer’s disease genotypes, phenotype, and treatments. Science 275(5300): 630-1.(1997);
[5]
Kuszczyk M, Gordon-Krajcer W, Lazarewicz JW. Homocysteine-induced acute excitotoxicity in cerebellar granule cells in vitro is accompanied by PP2A-mediated dephosphorylation of tau. Neurochem Int 55(1-3): 174-80.(2009);
[6]
Wilquet V, De Strooper B. Amyloid-beta precursor protein processing in neurodegeneration. Curr Opin Neurobiol 14(5): 582-8.(2004);
[7]
Gruden MA, Davidova TB, Mališauskas M, Sewell RDE, Voskresenskaya NI, Wilhelm K, et al. Differential neuroimmune markers to the onset of Alzheimer’s disease neurodegeneration and dementia: Autoantibodies to Aβ (25-35) oligomers, S100b and neurotransmitters. J Neuroimmunol 186(1-2): 181-92.(2007);
[8]
Selkoe DJ. Alzheimer’s disease: Genes, proteins, and therapy. Physiol Rev 81(2): 741-66.(2001);
[9]
Benzi G, Moretti A. Are reactive oxygen species involved in Alzheimer’s disease? Neurobiol Aging 16(4): 661-74.(1995);
[10]
Mark RJ, Hensley K, Butterfield DA, Mattson MP. Amyloid β-peptide impairs ion-motive ATPase activities: evidence for a role in loss of neuronal Ca2+ homeostasis and cell death. J Neurosci 15(9): 6239-49.(1995);
[11]
Niu B, Zhao M, Su Q, Zhang M, Lv W, Chen Q, et al. 2D-SAR and 3D-QSAR analyses for acetylcholinesterase inhibitors. Mol Divers Mol Divers 21(2): 413-26.(2017);
[12]
Wang B, Lu K, Zheng X, Su B, Zhou Y, Chen P, et al. Early stage identification of alzheimer’s disease using a two-stage ensemble classifier. Curr Bioinform 13(5): 529-35.(2018);
[13]
Hu Y, Zhou G, Zhang C, Zhang M, Chen Q, Zheng L, et al. Identify compounds’ target against Alzheimer’s disease based on in-silico approach. Curr Alzheimer Res 16(3): 193-208.(2019);
[14]
Wang H, Li R, Shen Y. β-Secretase: its biology as a therapeutic target in diseases. Trends Pharmacol Sci 34(4): 215-25.(2013);
[15]
Tesco G, Koh YH, Kang EL, Cameron AN, Das S, Sena-Esteves M, et al. Depletion of GGA3 stabilizes BACE and enhances β-secretase activity. Neuron 54(5): 721-37.(2007);
[16]
Kametaka S, Shibata M, Moroe K, Kanamori S, Ohsawa Y, Waguri S, et al. Identification of phospholipid scramblase 1 as a novel interacting molecule with β-secretase (β-site amyloid precursor protein (APP) cleaving enzyme (BACE)). J Biol Chem 278(17): 15239-45.(2003);
[17]
Spoelgen R, von Arnim CAF, Thomas AV, Peltan ID, Koker M, Deng A, et al. Interaction of the cytosolic domains of sorLA/LR11 with the amyloid precursor protein (APP) and β-secretase β-site APP-cleaving enzyme. J Neurosci 26(2): 418-28.(2006);
[18]
He W, Lu Y, Qahwash I, Hu XY, Chang A, Yan R. Reticulon family members modulate BACE1 activity and amyloid-β peptide generation. Nat Med 10(9): 959-65.(2004);
[19]
Ghosh AK, Shin D, Downs D, Koelsch G, Lin X, Ermolieff J, et al. Design of potent inhibitors for human brain memapsin 2 (β-secretase). J Am Chem Soc 122(14): 3522-3.(2000);
[20]
Byun HG, Kim YT, Park PJ, Lin X, Kim SK. Chitooligosaccharides as a novel β-secretase inhibitor. Carbohydr Polym 61(2): 198-202.(2005);
[21]
Rezai-Zadeh K, Shytle D, Sun N, Mori T, Hou H, Jeanniton D, et al. Green tea epigallocatechin-3-gallate (EGCG) modulates amyloid precursor protein cleavage and reduces cerebral amyloidosis in Alzheimer transgenic mice. J Neurosci 25(38): 8807-14.(2005);
[22]
Kwak HM, Jeon SY, Sohng BH, Kim JG, Lee JM, Lee KB, et al. β-secretase (BACE1) inhibitors from pomegranate (Punica granatum) husk. Arch Pharm Res 28(12): 1328-32.(2005);
[23]
Park IH, Jeon SY, Lee HJ, Kim SI, Song KS. A β-secretase (BACE1) inhibitor hispidin from the mycelial cultures of Phellinus linteus. Planta Med 70(2): 143-6.(2004);
[24]
Lee HJ, Seong YH, Bae KH, Kwon SH, Kwak HM, Nho SK, et al. β-secretase (BACE1) inhibitors from sanguisorbae radix. Arch Pharm Res Arch Pharm Res 28(7): 799-803.(2005);
[25]
Abuine R, Rathnayake AU, Byun HG. Biological activity of peptides purified from fish skin hydrolysates. Fish Aquat Sci 22(1): 1-14.(2019);
[26]
Cheung IWY, Cheung LKY, Tan NY, Li-Chan ECY. The role of molecular size in antioxidant activity of peptide fractions from Pacific hake (Merluccius productus) hydrolysates. Food Chem 134(3): 1297-306.(2012);
[27]
Mendis E, Rajapakse N, Kim SK. Antioxidant properties of a radical-scavenging peptide purified from enzymatically prepared fish skin gelatin hydrolysate. J Agric Food Chem 53(3): 581-7.(2005);
[28]
McLay RN, Pan W, Kastin AJ. Effects of peptides on animal and human behavior: a review of studies published in the first twenty years of the journal Peptides. Peptides 22(12): 2181-255.(2001);
[29]
Lee JK, Li-Chan ECYY, Byun H-GG. Characterization of β-secretase inhibitory peptide purified from skate skin protein hydrolysate. Eur Food Res Technol 240(1): 129-36.(2014);
[30]
Li-Chan ECY, Cheung IWY, Byun HG. Shrimp (Pandalopsis dispar) waste hydrolysate as a source of novel β-secretase inhibitors. Fish Aquat Sci 19(2)(2016);
[31]
Lee JK, Kim SR, Byun H-G. Characterization of β-secretase inhibitory peptide purified from blackfin flounder (glyptocephalus stelleri) protein hydrolysate. Eur Food Res Technol 10(1): 1-8.(2018);
[32]
Lee JK, Kim SR, Byun HG. Purification and characterization of β- secretase inhibitory peptide from sea hare (Aplysia kurodai) by enzymatic hydrolysis. Fish Aquat Sci 21(3)(2018);
[33]
Samaranayaka AGP, Ho TCW, Li-Chan ECY. Correlation of Kudoa spore counts with proteolytic activity and texture of fish mince from pacific hake (Merluccius productus). J Aquat Food Prod Technol 15(4): 75-93.(2006);
[34]
Johnston JA, Liu WW, Coulson DTR, Todd S, Murphy S, Brennan S, et al. Platelet β-secretase activity is increased in Alzheimer’s disease. Neurobiol Aging 29(5): 661-8.(2008);
[35]
Jämsä A, Belda O, Edlund M, Lindström E. BACE-1 inhibition prevents the -secretase inhibitor evoked A rise in human neuroblastoma SH-SY5Y cells. J Biomed Sci 18: 76.(2011);
[36]
Lee DH, Lee DH, Lee JS. Characterization of a new antidementia β-secretase inhibitory peptide from Saccharomyces cerevisiae. Enzyme Microb Technol 42(1): 83-8.(2007);
[37]
Kimura T, Shuto D, Kasai S, Liu P, Hidaka K, Hamada T, et al. KMI-358 and KMI-370, highly potent and small-sized BACE1 inhibitors containing phenylnorstatine. Bioorg Med Chem Lett 14(6): 1527-31.(2004);
[38]
Shuto D, Kasai S, Kimura T, Liu P, Hidaka K, Hamada T, et al. KMI-008, a novel β-Secretase inhibitor containing a hydroxymethylcarbonyl isostere as a transition-State mimic: Design and synthesis of substrate-based octapeptides. Bioorganic Bioorg Med Chem Lett 13(24): 4273-6.(2003);
[39]
Wu YJ, Guernon J, Yang F, Snyder L, Shi J, McClure A, et al. Targeting the BACE1 active site flap leads to a potent inhibitor that elicits robust brain Aβ reduction in rodents. ACS Med Chem Lett 7(3): 271-6.(2016);
[40]
Schechter I, Berger A. On the active site of proteases. III. Mapping the active site of papain; specific peptide inhibitors of papain. Biochem Biophys Res Commun 32(5): 898-902.(1968);
[41]
Ghosh AK, Osswald HL. BACE1 (β-secretase) inhibitors for the treatment of Alzheimer’s disease. Chem Soc Rev 43(19): 6765-813.(2014);
[42]
Kim J, Lee HJ, Lee KW. Naturally occurring phytochemicals for the prevention of Alzheimer’s disease. J Neurochem 112(6): 1415-30.(2010);
[43]
Rathnayake AU, Abuine R, Kim YJ, Byun HG. Anti-Alzheimer’s materials isolated from marine bio-resources: a review. Curr Alzheimer Res (2019). [Epub ahead of print].


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Article Details

VOLUME: 16
ISSUE: 11
Year: 2019
Page: [1028 - 1038]
Pages: 11
DOI: 10.2174/1567205016666191113122046
Price: $65

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