In vivo analysis using a presenilin-1-specific inhibitor: Presenilin1-containing λ-secretase complexes mediate the majority of CNS Aβ production in the mouse

Alzheimer's Disease Research Journal

Volumn 3, Issue 1, 2011, Pages 29-45

  Borgegård, Tomas ^a   Minidis, Alexander ^b   Jureus, Anders ^a   Malmborg, Jonas ^c   Rosqvist, Susanne ^a   Gruber, Susanne ^a   Almqvist, Helena ^a   Yan, Hongmei ^c   Bogstedt, Anna ^a   Olsson, Fredrik ^a   Dahlström, Jessie ^c   Ray, Colin ^b   Närhi, Katja ^b   Malinowsky, David ^a   Hagström, Elin ^a   Jin, Shaobo ^d   Malmberg, Åsa ^a   Lendahl, Urban ^d   Lundkvist, Johan ^a  

^a ASTRAZENECA R AND D   (Sweden)

^b Med Chem Dept   (Sweden)

^c DMPK Dept   (Sweden)

^d KAROLINSKA INSTITUTE   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN; GAMMA SECRETASE; GAMMA SECRETASE INHIBITOR; PRESENILIN 1; PRESENILIN 2; UNCLASSIFIED DRUG; ZI 10;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; C57BL 6 MOUSE; CELL LYSATE; CENTRAL NERVOUS SYSTEM; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG POTENCY; DRUG STRUCTURE; FEMALE; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; IN VIVO STUDY; MALE; MOUSE; NONHUMAN; PROTEIN BLOOD LEVEL; PROTEIN SYNTHESIS INHIBITION; RAT; STRUCTURE ANALYSIS;

EID: 82755187127     PISSN: 19352514     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (30)

1. Beher, D., Fricker, M., Nadin, A., Clarke, E. E., Wrigley, J. D., Li, Y. M., Culvenor, J. G., Masters, C. L., Harrison, T. and Shearman, M. S. (2003). In vitro characterization of the presenilin-dependent gamma-secretase complex using a novel affinity ligand. Biochemistry 42, 8133-42.
2. Bentahir, M., Nyabi, O., Verhamme, J., Tolia, A., Horre, K., Wiltfang, J., Esselmann, H. and De Strooper, B. (2006). Presenilin clinical mutations can affect gamma-secretase activity by different mechanisms. J. Neurochem 96, 732-42.
3. Brown, M. S. and Goldstein, J. L. (1997). The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell 89, 331-40.
4. 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. et al. (2008). The amyloid-beta rise and gamma-secretase inhibitor potency depend on the level of substrate expression. J. Biol Chem 283, 22992-3003.
5. Deane, R., Bell, R. D., Sagare, A. and Zlokovic, B. V. (2009). Clearance of amyloid-beta peptide across the blood-brain barrier: implication for therapies in Alzheimer's disease. CNS Neurol Disord Drug Targets 8, 16-30.
6. Dejaegere, T., Serneels, L., Schafer, M. K., Van Biervliet, J., Horre, K., Depboylu, C., Alvarez-Fischer, D., Herreman, A., Willem, M., Haass, C. et al. (2008). Deficiency of Aph1B/C-gamma-secretase disturbs Nrg1 cleavage and sensorimotor gating that can be reversed with antipsychotic treatment. Proc. Natl. Acad. Sci. USA 105, 9775-80.
7. Donoviel, D. B., Hadjantonakis, A. K., Ikeda, M., Zheng, H., Hyslop, P. S. and Bernstein, A. (1999). Mice lacking both presenilin genes exhibit early embryonic patterning defects. Genes Dev. 13, 2801-10.
8. Ehrmann, M. and Clausen, T. (2004). Proteolysis as a regulatory mechanism. Annu. Rev. Genet. 38, 709-24.
9. Friden, M., Ducrozet, F., Middleton, B., Antonsson, M., Bredberg, U. and Hammarlund-Udenaes, M. (2009). Development of a high-throughput brain slice method for studying drug distribution in the central nervous system. Drug Metab. Dispos. 37, 1226-33.
10. Fuwa, H., Takahashi, Y., Konno, Y., Watanabe, N., Miyashita, H., Sasaki, M., Natsugari, H., Kan, T., Fukuyama, T., Tomita, T. et al. (2007). Divergent synthesis of multifunctional molecular probes to elucidate the enzyme specificity of dipeptidic gamma-secretase inhibitors. ACS Chem. Biol. 2, 408-18.
11. Gotz, J., Chen, F., van Dorpe, J. and Nitsch, R. M. (2001). Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils. Science 293, 1491-5.
12. Henley, D. B., May, P. C., Dean, R. A. and Siemers, E. R. (2009). Development of semagacestat (LY450139), a functional gamma-secretase inhibitor, for the treatment of Alzheimer's disease. Expert Opin. Pharmacother 10, 1657-64.
13. Herreman, A., Hartmann, D., Annaert, W., Saftig, P., Craessaerts, K., Serneels, L., Umans, L., Schrijvers, V., Checler, F., Vanderstichele, H. et al. (1999). Presenilin 2 deficiency causes a mild pulmonary phenotype and no changes in amyloid precursor protein processing but enhances the embryonic lethal phenotype of presenilin 1 deficiency. Proc. Natl. Acad. Sci. USA 96, 11872-7.
14. Herreman, A., Serneels, L., Annaert, W., Collen, D., Schoonjans, L. and De Strooper, B. (2000). Total inactivation of gamma-secretase activity in presenilin-deficient embryonic stem cells. Nat. Cell Biol 2, 461-2.
15. Jack, C. R., Jr., Knopman, D. S., Jagust, W. J., Shaw, L. M., Aisen, P. S., Weiner, M. W., Petersen, R. C. and Trojanowski, J. Q. (2010). Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol 9, 119-28.
16. 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. et al. (2000). Photoactivated gamma-secretase inhibitors directed to the active site covalently label presenilin 1. Nature 405, 689-94.
17. Lundkvist, J. and Naslund, J. (2007). Gamma-secretase: a complex target for Alzheimer's disease. Curr. Opin. Pharmacol 7, 112-8.
18. Martone, R. L., Zhou, H., Atchison, K., Comery, T., Xu, J. Z., Huang, X., Gong, X., Jin, M., Kreft, A., Harrison, B. et al. (2009). Begacestat (GSI-953): a novel, selective thiophene sulfonamide inhibitor of amyloid precursor protein gamma-secretase for the treatment of Alzheimer's disease. J. Pharmacol. Exp. Ther 331, 598-608.
19. Oddo, S., Billings, L., Kesslak, J. P., Cribbs, D. H. and LaFerla, F. M. (2004). Abeta immunotherapy leads to clearance of early, but not late, hyperphosphorylated tau aggregates via the proteasome. Neuron 43, 321-32.
20. Saura, C. A., Choi, S. Y., Beglopoulos, V., Malkani, S., Zhang, D., Shankaranarayana Rao, B. S., Chattarji, S., Kelleher, R. J., 3rd, Kandel, E. R., Duff, K. et al. (2004). Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration. Neuron 42, 23-36.
21. Seiffert, D., Bradley, J. D., Rominger, C. M., Rominger, D. H., Yang, F., Meredith, J. E., Jr., Wang, Q., Roach, A. H., Thompson, L. A., Spitz, S. M. et al. (2000). Presenilin-1 and -2 are molecular targets for gamma-secretase inhibitors. J. Biol. Chem. 275, 34086-91.
22. Serneels, L., Dejaegere, T., Craessaerts, K., Horre, K., Jorissen, E., Tousseyn, T., Hebert, S., Coolen, M., Martens, G., Zwijsen, A. et al. (2005). Differential contribution of the three Aph1 genes to gamma-secretase activity in vivo. Proc. Natl. Acad. Sci. USA 102, 1719-24.
23. Shirotani, K., Tomioka, M., Kremmer, E., Haass, C. and Steiner, H. (2007). Pathological activity of familial Alzheimer's disease-associated mutant presenilin can be executed by six different gamma-secretase complexes. Neurobiol. Dis. 27, 102-7.
24. St George-Hyslop, P. H. and Petit, A. (2005). Molecular biology and genetics of Alzheimer's disease. C R Biol. 328, 119-30.
25. Stromberg, K., Hansson, E. M., Laudon, H., Bergstedt, S., Naslund, J., Lundkvist, J. and Lendahl, U. (2005). Gamma-Secretase complexes containing N- and C-terminal fragments of different presenilin origin retain normal gamma-secretase activity. J. Neurochem. 95, 880-90.
26. 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 non-competitive inhibition of solubilized human gamma-secretase by pepstatin A methylester, L685458, sulfonamides, and benzodiazepines. J. Biol. Chem. 277, 31499-505.
27. Wolfe, M. S. (2007). When loss is gain: reduced presenilin proteolytic function leads to increased Abeta42/Abeta40. Talking Point on the role of presenilin mutations in Alzheimer disease. EMBO Rep 8, 136-40.
28. Wolfe, M. S. and Kopan, R. (2004). Intramembrane proteolysis: theme and variations. Science 305, 1119-23.
29. Yu, H., Saura, C. A., Choi, S. Y., Sun, L. D., Yang, X., Handler, M., Kawarabayashi, T., Younkin, L., Fedeles, B., Wilson, M. A. et al. (2001). APP processing and synaptic plasticity in presenilin-1 conditional knockout mice. Neuron 31, 713-26.
30. Zhao, B., Yu, M., Neitzel, M., Marugg, J., Jagodzinski, J., Lee, M., Hu, K., Schenk, D., Yednock, T. and Basi, G. (2008). Identification of gamma-secretase inhibitor potency determinants on presenilin. J. Biol. Chem. 283, 2927-38.