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Effects of 3-Phenyl-1-isoquinolinamine on the Metabolism of ${\beta}$-Amyloid Precursor Protein in Neuroblastoma Cells  

Leem, Jae-Yoon (College of Pharmacy, Woosuk University)
Cho, Won-Jea (College of Pharmacy and Research Institute of Drug Development, Chonnam National University)
Publication Information
YAKHAK HOEJI / v.54, no.6, 2010 , pp. 529-534 More about this Journal
Abstract
Alzheimer's disease (AD) is characterized pathologically by the presence of intracellular neurofibrillary tangles and deposition of ${\beta}$-amyloid ($A{\beta}$) peptides, which are generated by processing of amyloid precursor protein (APP). It is urgent to develop effective therapies for the treatment of AD, since our society rapidly accelerate aging. $A{\beta}$ peptides have been believed to be neurotoxic and now are also considered to have effects on the mechanism of memory formation. Recently, we investigated that a quinoline compound from natural product reduced the secretion of $A{\beta}$ from the neuroblastoma N2a cells (NL/N cell line) overexpressing APPswe. In this study, 3-phenyl-1-isoquinolinamine, a synthetic isoquinoline compound was analyzed to determine its effects on the metabolism of APP. It inhibited the secretion of $A{\beta}$ peptides from the N2a NL/N cell line. Beta-site APP cleaving enzyme (BACE) fluorescence resonance energy transfer (FRET) assay revealed that it inhibited BACE activity in a dose dependent manner. Immunoblotting study showed that it inhibited APP stabilization and expression and it slightly increased the stablization and the expression of ${\gamma}$-secreatase component from the N2a NL/N cell line. We suggest that 3-phenyl-1-isoquinolinamine inhibits APP metabolism and $A{\beta}$ generation by the means of BACE inhibitory mechanism. This is the first report that 3-phenyl-1-isoquinolinamine inhibits the secretion of $A{\beta}$ peptides from neuroblastoma cells.
Keywords
Alzheimer's disease; ${\beta}$-amyloid peptides; APPswe; 3-phenyl-1-isoquinolinamine; BACE;
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1 Nunan, J. and Small, D. H. : Regulation of APP cleavage by ${\alpha}-,\;{\beta}-\;and\;{\gamma}$-secretases. FEBS Lett. 483, 6 (2000).   DOI   ScienceOn
2 Cho, W. J., Min, S. Y., Le, T. N. and Kim, T. S. : Synthesis of new 3-arylisoquinolinamines: effect on topoisomerase I inhibition and cytotoxicity. Bioorg. Med. Chem. Lett. 13, 4451 (2003).   DOI   ScienceOn
3 Wang, R., Sweeney, D., Gandy, S. E. and Sissodia, S. S. : The profile of soluble amyloid $\beta$ protein in cultured cell media. J. Biol. Chem. 271, 31894 (1996).   DOI   ScienceOn
4 Tung, J. S., Davis, D. L., Anderson, J. P., Walker, D. E., Mamo, S., Jewett, N., Hom, R. K., Sinha, S., Thorsett, E. D. and John, V. : Design of substrate-based inhibitors of human $\beta$-secretase. J. Med. Chem. 45, 259 (2002).   DOI   ScienceOn
5 Kinoshita, A., Fukumoto, H., Shah, T., Whelan, C. M., Irizarry, M. C. and Hyman, B. T. : Demonstration by FRET of BACE interaction with the amyloid precursor protein at the cell surface and in early endosomes. J. Cell. Sci. 116, 3339 (2003).   DOI   ScienceOn
6 Leem, J. Y., Saura, C. A., Pietrzik, C., Christianson, J., Wanamaker, C., King, L. T., Veselits, M. L., Tomita, T., Gasparini, L., Iwatsubo, T., Xu, H., Green, W. N., Koo, E. H. and Thinakaran, G. : A role for presenilin 1 in regulating the delivery of amyloid precursor protein to the cell surface. Neurobiol. Dis. 11, 64 (2002).   DOI   ScienceOn
7 Citron, M., Westaway, D., Xia, W., Carlson, G., Diehl, T., Levesque, G., Johnson-Wood, K., Lee, M., Seubert, P., Davis, A., Kholodenko, D., Motter, R., Sherrington, R., Perry, B., Yao, H., Strome, R., Lieberburg, I. Rommens, J., Kim, S., Schenk, D., Fraser, P., St George Hyslop, P. and Selkoe. D. J. : Mutant presenilins of Alzheimer's disease increase production of 42- residue amyloid $\beta$-protein in both transfected cells and transgenic mice, Nat. Med. 3, 67 (1997).   DOI   ScienceOn
8 Yu, G., Nishimura, M., Arawaka, S., Levitan, D., Zhang, L., Tandon, A., Song, Y. Q., Rogaeva, E., Chen, F., Kawarai, T., Supala, A., Levesque, L., Yu, H., Yang, D. S., Holmes, E., Milman, P., Liang, Y., Zhang, D. M., Xu, D. H., Sato, C., Rogaev, E., Smith, M., Janus, C., Zhang, Y., Aebersold, R., Farrer, L. S., Sorbi, S., Bruni, A., Fraser, P. and St. George-Hyslop, P. : Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and ${\beta}APP $ processing. Nature 407, 48 (2000).   DOI   ScienceOn
9 Lee, S. F., Shah, S., Li, H., Yu, C., Han, W. and Yu, G. : Mammalian APH-1 interacts with presenilin and nicastrin and is required for intramembrane proteolysis of amyloid-$\beta$ precursor protein and Notch. J. Biol. Chem. 277, 45013 (2002).   DOI   ScienceOn
10 Steiner, H., Winkler, E., Edbauer, D., Prokop, S., Basset, G., Yamasaki, A., Kostka, M. and Haass, C. : PEN-2 is an integral component of the $\gamma$-secretase complex required for coordinated expression of presenilin and nicastrin. J. Biol. Chem. 277, 39062 (2002).   DOI   ScienceOn
11 Strittmatter, W. J., Weisgraber, K. H., Huang, D. Y., Dong, L. M., Salvesen, G. S., Pericak-Vance, M., Schmechel, D., Saunders, A. M., Goldgaber, D. and Roses, A. D. : Binding of human apolipoprotein E to synthetic amyloid beta peptide isoform-specific effects and implications for late-onset Alzheimer disease. Proc. Natl. Acad. Sci. USA 90, 8098 (1993).   DOI   ScienceOn
12 Hardy, J. and Selkoe, D. J. : The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297, 353 (2002).   DOI   ScienceOn
13 Cai, H., Wang, Y., McCarthy, D., Wen, H., Borchelt, D. R., Price, D. L. and Wong, P. C. : BACE1 is the major -secretase for generation of A peptides by neurons. Nature Neurosci. 4, 233 (2001).   DOI   ScienceOn
14 Leem, J. Y., et al. : Effect of a quinoline compound from the oriental medicine on the metabolism of $\beta$-amyloid precursor protein in neuroblastoma cells. (manuscript in preparation).
15 Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L. and Pericak-Vance, M. A. : Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 261, 921 (1993).   DOI
16 Vassar, R., Bennett, B. D., Babu-Khan, S., Kahn, S., Mendiaz, E. A., Denis, P., Teplow, D. B., Ross, S., Amarante, P., Loeloff, R., Luo, Y., Fisher, S., Fuller, J., Edenson, S., Lile, J., Jarosinski, M. A., Biere, A. L., Curran, E., Burgess, T., Louis, J. C., Collins, F., Treanor, J., Rogers, G. and Citron, M. : $\beta$-Secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286, 735 (1999).   DOI   ScienceOn
17 Selkoe, D. J. : Translating cell biology into therapeutic advances in Alzheimer's disease. Nature 399, 23 (1999).   DOI   ScienceOn
18 Morris, J. C. : Classification of dementia and Alzheimer's disease. Acta Neurol. Scand. 165, 41 (1996).
19 Jann, M. W. : Rivastigmine, a new-generation cholinesterase inhibitor for the treatment of Alzheimer's disease. Pharmacotherapy 20, 1 (2000).   DOI   ScienceOn
20 Iqbal, K., Sisodia, S. S. and Winblad, B. : Alzheimer's disease: Advances in etionlogy, pathogenesis and therapeutics. John Wiley & Sons, Ltd. (2001).
21 Braak, H., Braak, E. and Strothjohann, M. : Abnormally phosphorylated tau protein related to the formation of neurofibrillary tangles and neuropil threads in the cerebral cortex of sheep and goat. Neurosci Lett. 171, 1 (1994).   DOI   ScienceOn
22 Kang, J., Lemaire, H. G., Unterbeck, A., Salbaum, J. M., Masters, C. L., Grzeschik, K. H., Multhaup, G., Beyreuther, K. and Muller-Hill, B. : The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature 325, 733 (1987).   DOI   ScienceOn
23 Selkoe, D. J. : The cell biology of beta-amyloid precursor protein and presenilin in Alzheimer's disease. Trends Cell Biol. 8, 447 (1998).   DOI   ScienceOn
24 Takahashi, Y., Hayashi, I., Tominari, Y., Rikimaru, K., Morohashi, Y., Kan, T., Natsugari, H., Fukuyama, T., Tomita, T. and Iwatsubo, T. : Sulindac sulfide is a noncompetitive $\gamma$-secretase inhibitor that preferentially reduces $A{\beta}$ 42 generation. J. Biol. Chem. 278, 18664 (2003).   DOI   ScienceOn
25 Bertram, L., Lill, C. M. and Tanzi, R. E. : The genetics of Alzheimer disease: back to the future. Neuron. 68, 270 (2010).   DOI   ScienceOn
26 Sugimoto, H. : Donepezil hydrochloride: a treatment drug for Alzheimer's disease. Chem. Rec. 1, 63 (2001).   DOI   ScienceOn
27 Zarotsky, V., Sramek, J. J., and Cutler, N. R. : Galantamine hydrobromide: an agent for Alzheimer's disease. Am. J. Health Syst. Pharm. 60, 446 (2003).
28 Kulkarni, S. K. and Dhir, A. : Berberine, a plant alkaloid with therapeutic potential for central nervous system disorders. Phytother Res. 24, 317 (2010).   DOI   ScienceOn
29 Jung, H. A., Min, B. S., Yokozawa, T., Lee, J. H., Kim, Y. S. and Choi, J. S. : Anti-Alzheimer and antioxidant activities of Coptidis Rhizoma alkaloids. Biol. Pharm. Bull. 32, 1433 (2009).   DOI   ScienceOn
30 Kuo, Y. M., Emmerling, M. R., Vigo-Pelfrey, C., Kasunic, T. C., Kirkpatrick, J. B., Murdoch, G. H., Ball, M. J. and Roher, A. E. : Water-soluble $A{\beta}$ (N-40, N-42) oligomers in normal and Alzheimer disease brains. J. Biol. Chem. 271, 4077 (1996).   DOI
31 Sambamurti, K., Hardy, J., Refolo L. M. and Lahiri, D. K. : Targeting APP metabolism for the treatment of Alzheimer's disease. Drug Dev. Res. 56, 211 (2002).   DOI   ScienceOn
32 Skovronsky, D. M., Moore, D. B., Milla, M. E., Doms, R. W. and Lee, V. M. : Protein kinase C-dependent $\alpha$-secretase competes with $\beta$-secretase for cleavage of amyloid-$\beta$ precursor protein in the trans-golgi network. J. Biol. Chem. 275, 2568 (2000).   DOI   ScienceOn