Interplay between α-, β-, and γ-secretases determines biphasic amyloid-β protein level in the presence of a γ-secretase inhibitor

Journal of Biological Chemistry

Volumn 288, Issue 2, 2013, Pages 785-792

  Ortega, Fernando ^a   Stott, Jonathan ^a   Visser, Sandra A G ^b   Bendtsen, Claus ^a  

^a ASTRAZENECA   (United Kingdom)

^b ASTRAZENECA R AND D   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

ALZHEIMER DISEASE; AMYLOID PRECURSOR PROTEINS; ANIMAL MODEL; CELL LINES; IN-VITRO; IN-VIVO; INHIBITOR CONCENTRATION; MECHANISTIC MODELS; PROTEIN LEVEL; SECRETASES;

CELL CULTURE; MATHEMATICAL MODELS; NEURODEGENERATIVE DISEASES;

GLYCOPROTEINS;

ALPHA SECRETASE; AMYLOID BETA PROTEIN; AMYLOID BETA PROTEIN[1-40]; AMYLOID BETA PROTEIN[1-42]; AMYLOID PRECURSOR PROTEIN; BETA SECRETASE; GAMMA SECRETASE; GAMMA SECRETASE INHIBITOR; SEMAGACESTAT;

ARTICLE; CELL LINE; CONCENTRATION RESPONSE; EMBRYO; ENZYME ACTIVITY; HUMAN; HUMAN CELL; HUMAN EXPERIMENT; IN VITRO STUDY; MATHEMATICAL MODEL; NORMAL HUMAN; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTEIN CLEAVAGE; PROTEIN PROCESSING; PROTEIN SYNTHESIS; QUANTITATIVE ANALYSIS; SIGNAL TRANSDUCTION; SINGLE DRUG DOSE;

AMYLOID BETA-PEPTIDES; AMYLOID PRECURSOR PROTEIN SECRETASES; CELL LINE; ENZYME INHIBITORS; HUMANS;

ANIMALIA;

EID: 84872330749     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M112.419135     Document Type: Article

References (41)

1. Selkoe, D. J., and Schenk, D. (2003) Alzheimer's disease: molecular understanding predicts amyloid-based therapeutics. Annu. Rev. Pharmacol. Toxicol. 43, 545-584 (Pubitemid 37372653)
2. Korczyn, A. D. (2008) The amyloid cascade hypothesis. Alzheimers Dement. 4, 176-178
3. De Strooper, B. (2010) Proteases and proteolysis in Alzheimer disease: a multifactorial view on the disease process. Physiol. Rev. 90, 465-494
4. Prox, J., Rittger, A., and Saftig, P. (2012) Physiological functions of the amyloid precursor protein secretases ADAM10, BACE1, and Presenilin. Exp. Brain Res. 217, 331-341
5. Citron, M., Oltersdorf, T., Haass, C., McConlogue, L., Hung, A. Y., Seubert, P., Vigo-Pelfrey, C., Lieberburg, I., and Selkoe, D. J. (1992) Mutation of the β-amyloid precursor protein in familial Alzheimer's disease increases β-protein production. Nature 360, 672-674 (Pubitemid 23007680)
6. Kuhn, P. H., Wang, H., Dislich, B., Colombo, A., Zeitschel, U., Ellwart, J. W., Kremmer, E., Rossner, S., and Lichtenthaler, S. F. (2010) ADAM10 is the physiologically relevant, constitutive α-secretase of the amyloid precursor protein in primary neurons. EMBO J. 29, 3020-3032
7. Asai, M., Hattori, C., Szabó, B., Sasagawa, N., Maruyama, K., Tanuma, S., and Ishiura, S. (2003) Putative function of ADAM9, ADAM10, and ADAM17 as APP α-secretase. Biochem. Biophys. Res. Commun. 301, 231-235 (Pubitemid 36268873)
8. 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. (1999) β-Secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286, 735-741
9. Yagishita, S., Morishima-Kawashima, M., Tanimura, Y., Ishiura, S., and Ihara, Y. (2006) DAPT-induced intracellular accumulations of longer amyloid β-proteins: further implications for the mechanism of intramembrane cleavage by γ-secretase. Biochemistry 45, 3952-3960
10. Zhang, L., Song, L., Terracina, G., Liu, Y., Pramanik, B., and Parker, E. (2001) Biochemical characterization of the γ-secretase activity that produces β-amyloid peptides. Biochemistry 40, 5049-5055 (Pubitemid 32332551)
11. Jäger, S., Leuchtenberger, S., Martin, A., Czirr, E., Wesselowski, J., Dieckmann, M., Waldron, E., Korth, C., Koo, E. H., Heneka, M., Weggen, S., and Pietrzik, C. U. (2009) α-Secretase mediated conversion of the amyloid precursor protein derived membrane stub C99 to C83 limits Aβ generation. J. Neurochem. 111, 1369-1382
12. Siemers, E. R., Dean, R. A., Friedrich, S., Ferguson-Sells, L., Gonzales, C., Farlow, M. R., and May, P. C. (2007) Safety, tolerability, and effects on plasma and cerebrospinal fluid amyloid-β after inhibition of γ-secretase. Clin. Neuropharmacol. 30, 317-325 (Pubitemid 350307310)
13. Burton, C. R., Meredith, J. E., Barten, D. M., Goldstein, M. E., Krause, C. M., Kieras, C. J., Sisk, L., Iben, L. G., Polson, C., Thompson, M. W., Lin, X. A., Corsa, J., Fiedler, T., Pierdomenico, M., Cao, Y., Roach, A. H., Cantone, J. L., Ford, M. J., Drexler, D. M., Olson, R. E., Yang, M. G., Bergstrom, C. P., McElhone, K. E., Bronson, J. J., Macor, J. E., Blat, Y., Grafstrom, R. H., Stern, A. M., Seiffert, D. A., Zaczek, R., Albright, C. F., and Toyn, J. H. (2008) The amyloid-β rise and γ-secretase inhibitor potency depend on the level of substrate expression. J. Biol. Chem. 283, 22992-23003
14. Wolfe, M. S., Citron, M., Diehl, T. S., Xia, W., Donkor, I. O., and Selkoe, D. J. (1998) A substrate-based difluoro ketone selectively inhibits Alzheimer's γ-secretase activity. J. Med. Chem. 41, 6-9
15. 42/40 ratio. PLoS One 4, e7893
16. McLendon, C., Xin, T., Ziani-Cherif, C., Murphy, M. P., Findlay, K. A., Lewis, P. A., Pinnix, I., Sambamurti, K., Wang, R., Fauq, A., and Golde, T. E. (2000) Cell-free assays for γ-secretase activity. FASEB J. 14, 2383-2386
17. Martone, R. L., Zhou, H., Atchison, K., Comery, T., Xu, J. Z., Huang, X., Gong, X., Jin, M., Kreft, A., Harrison, B., Mayer, S. C., Aschmies, S., Gonzales, C., Zaleska, M. M., Riddell, D. R., Wagner, E., Lu, P., Sun, S. C., Sonnenberg-Reines, J., Oganesian, A., Adkins, K., Leach, M. W., Clarke, D. W., Huryn, D., Abou-Gharbia, M., Magolda, R., Bard, J., Frick, G., Raje, S., Forlow, S. B., Balliet, C., Burczynski, M. E., Reinhart, P. H., Wan, H. I., Pangalos, M. N., and Jacobsen, J. S. (2009) Begacestat (GSI-953): a novel, selective thiophene sulfonamide inhibitor of amyloid precursor protein γ-secretase for the treatment of Alzheimer's disease. J. Pharmacol. Exp. Ther. 331, 598-608
18. Li, Y. M., Xu, M., Lai, M. T., Huang, Q., Castro, J. L., DiMuzio-Mower, J., Harrison, T., Lellis, C., Nadin, A., Neduvelil, J. G., Register, R. B., Sardana, M. K., Shearman, M. S., Smith, A. L., Shi, X. P., Yin, K. C., Shafer, J. A., and Gardell, S. J. (2000) Photoactivated γ-secretase inhibitors directed to the active site covalently label presenilin 1. Nature 405, 689-694 (Pubitemid 30428655)
19. Osenkowski, P., Ye, W., Wang, R., Wolfe, M. S., and Selkoe, D. J. (2008) Direct and potent regulation of γ-secretase by its lipid microenvironment. J. Biol. Chem. 283, 22529-22540
20. Tian, G., Sobotka-Briner, C. D., Zysk, J., Liu, X., Birr, C., Sylvester, M. A., Edwards, P. D., Scott, C. D., and Greenberg, B. D. (2002) Linear noncompetitive inhibition of solubilized human γ-secretase by pepstatin A methylester, L685458, sulfonamides, and benzodiazepines. J. Biol. Chem. 277, 31499-31505 (Pubitemid 34968951)
21. Jämsä, A., Belda, O., Edlund, M., and Lindström, E. (2011) BACE-1 inhibition prevents the γ-secretase inhibitor evoked Aβ rise in human neuroblastoma SH-SY5Y cells. J. Biomed. Sci. 18, 76
22. Cook, J. J., Wildsmith, K. R., Gilberto, D. B., Holahan, M. A., Kinney, G. G., Mathers, P. D., Michener, M. S., Price, E. A., Shearman, M. S., Simon, A. J., Wang, J. X., Wu, G., Yarasheski, K. E., and Bateman, R. J. (2010) Acute γ-secretase inhibition of nonhuman primate CNS shifts amyloid precursor protein (APP) metabolism from amyloid-β production to alternative APP fragments without amyloid-β rebound. J. Neurosci. 30, 6743-6750
23. 1-[(7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl] -L-alaninamide (LY-411575). J. Pharmacol. Exp. Ther. 309, 49-55
24. Lu, Y., Zhang, L., Nolan, C. E., Becker, S. L., Atchison, K., Robshaw, A. E., Pustilnik, L. R., Osgood, S. M., Miller, E. H., Stepan, A. F., Subramanyam, C., Efremov, I., Hallgren, A. J., and Riddell, D. (2011) Quantitative pharmacokinetic/pharmacodynamic analyses suggest that 129/SVE mouse is a suitable preclinical pharmacology model for identifying small molecule γ-secretase inhibitors. J. Pharmacol. Exp. Ther. 339, 922-934
25. Prasad, C. V., Zheng, M., Vig, S., Bergstrom, C., Smith, D. W., Gao, Q., Yeola, S., Polson, C. T., Corsa, J. A., Guss, V. L., Loo, A., Wang, J., Sleczka, B. G., Dangler, C., Robertson, B. J., Hendrick, J. P., Roberts, S. B., and Barten, D. M. (2007) Discovery of (S)-2-((S)-2-(3,5-difluorophenyl)-2- hydroxyacetamido)-N-((S,Z)-3-methyl-4-oxo-4,5-dihydro-3Hbenzo[d][1,2] diazepin-5-yl)propanamide (BMS-433796): a γ-secretase inhibitor with Aβ lowering activity in a transgenic mouse model of Alzheimer's disease. Bioorg. Med. Chem. Lett. 17, 4006-4011 (Pubitemid 46920926)
26. Dockens, R., Wang, J. S., Castaneda, L., Sverdlov, O., Huang, S. P., Slemmon, R., Gu, H., Wong, O., Li, H., Berman, R. M., Smith, C., Albright, C. F., and Tong, G. (2012) Clin. Pharmacokinet. 51, 681-693
27. Kumamoto, M., Nakano, M., Uenaka, K., Lowe, S., Nishiuma, S., Nakamichi, N., Dean, R., Siemers, E., and Mohs, R. (2008) P4-379: Safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple-dose administration of a γ-secretase inhibitor in Japanese subjects. Alzheimers Dement. 4, T785
28. Niva, C., Parkinson, J., Olsson, F., van Schaick, E., Lundkvist, J., and Visser, S. A. G. (2012) Has inhibition of Aβ production adequately been tested as therapeutic approach in mild AD? A model-based meta-analysis of γ-secretase inhibitor data. (2013) Eur. J. Clin. Pharmacol., in press
29. Lanz, T. A., Karmilowicz, M. J., Wood, K. M., Pozdnyakov, N., Du, P., Piotrowski, M. A., Brown, T. M., Nolan, C. E., Richter, K. E. G., Finley, J. E., Fei, Q., Ebbinghaus, C. F., Chen, Y. L., Spracklin, D. K., Tate, B., Geoghegan, K. F., Lau, L. F., Auperin, D. D., and Schachter, J. B. (2006) Concentration-dependent modulation of amyloid-β in vivo and in vitro using the γ-secretase inhibitor, LY-450139. J. Pharmacol. Exp. Ther. 319, 924-933
30. Tomasselli, A. G., Qahwash, I., Emmons, T. L., Lu, Y., Leone, J. W., Lull, J. M., Fok, K. F., Bannow, C. A., Smith, C. W., Bienkowski, M. J., Heinrikson, R. L., and Yan, R. (2003) Employing a superior BACE1 cleavage sequence to probe cellular APP processing. J. Neurochem. 84, 1006-1017 (Pubitemid 36330654)
31. Barthet, G., Shioi, J., Shao, Z., Ren, Y., Georgakopoulos, A., and Robakis, N. K. (2011) Inhibitors of γ-secretase stabilize the complex and differentially affect processing of amyloid precursor protein and other substrates. FASEB J. 25, 2937-2946
32. Hook, V. Y., Kindy, M., and Hook, G. (2008) Inhibitors of cathepsin B improve memory and reduce β-amyloid in transgenic Alzheimer disease mice expressing the wild-type, but not the Swedish mutant, β-secretase site of the amyloid precursor protein. J. Biol. Chem. 283, 7745-7753
33. Hook, V., Schechter, I., Demuth, H. U., and Hook, G. (2008) Alternative pathways for production of β-amyloid peptides of Alzheimer's disease. Biol. Chem. 389, 993-1006
34. Durkin, J. T., Murthy, S., Husten, E. J., Trusko, S. P., Savage, M. J., Rotella, D. P., Greenberg, B. D., and Siman, R. (1999) Rank-order of potencies for inhibition of the secretion of Aβ40 and Aβ42 suggests that both are generated by a single γ-secretase. J. Biol. Chem. 274, 20499-20504
35. Das, R., Nachbar, R. B., Edelstein-Keshet, L., Saltzman, J. S., Wiener, M. C., Bagchi, A., Bailey, J., Coombs, D., Simon, A. J., Hargreaves, R. J., and Cook, J. J. (2011) Modeling effect of a γ-secretase inhibitor on amyloid-β dynamics reveals significant role of an amyloid clearance mechanism. Bull. Math. Biol. 73, 230-247
36. Fraering, P. C., Ye, W., LaVoie, M. J., Ostaszewski, B. L., Selkoe, D. J., and Wolfe, M. S. (2005) γ-Secretase substrate selectivity can be modulated directly via interaction with a nucleotide-binding site. J. Biol. Chem. 280, 41987-41996 (Pubitemid 43023167)
37. Bateman, R. J., Munsell, L. Y., Morris, J. C., Swarm, R., Yarasheski, K. E., and Holtzman, D. M. (2006) Human amyloid-β synthesis and clearance rates as measured in cerebrospinal fluid in vivo. Nat. Med. 12, 856-861 (Pubitemid 44050079)
38. Cirrito, J. R., May, P. C., O'Dell, M. A., Taylor, J. W., Parsadanian, M., Cramer, J. W., Audia, J. E., Nissen, J. S., Bales, K. R., Paul, S. M., DeMattos, R. B., and Holtzman, D. M. (2003) In vivo assessment of brain interstitial fluid with microdialysis reveals plaque-associated changes in amyloid-β metabolism and half-life. J. Neurosci. 23, 8844-8853 (Pubitemid 37210896)
39. Hone, E., Martins, I. J., Fonte, J., and Martins, R. N. (2003) Apolipoprotein E influences amyloid-β clearance from the murine periphery. J. Alzheimers Dis. 5, 1-8 (Pubitemid 36422845)
40. Ortega, F., Acerenza, L., Westerhoff, H. V., Mas, F., and Cascante, M. (2002) Product dependence and bifunctionality compromise the ultrasensitivity of signal transduction cascades. Proc. Natl. Acad. Sci. U.S.A. 99, 1170-1175 (Pubitemid 34136465)
41. Ortega, F., Garcés, J. L., Mas, F., Kholodenko, B. N., and Cascante, M. (2006) Bistability from double phosphorylation in signal transduction. FEBS J. 273, 3915-3926