Quantitative measurement of changes in amyloid-β(40) in the rat brain and cerebrospinal fluid following treatment with the γ-secretase inhibitor LY-411575 [N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N 1-[(7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl] -L-alaninamide]

Journal of Pharmacology and Experimental Therapeutics

Volumn 313, Issue 2, 2005, Pages 902-908

  Best, Jonathan D ^a   Jay, Mark T ^a   Otu, Franklin ^a   Ma, Jerome ^a   Nadin, Alan ^a   Ellis, Semantha ^a   Lewis, Huw D ^a   Pattison, Christine ^a   Reilly, Michael ^a   Harrison, Timothy ^a   Shearman, Mark S ^a   Williamson, Toni L ^a   Atack, John R ^a  

^a NEUROSCIENCE RESEARCH CENTRE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN[1-40]; AMYLOID PRECURSOR PROTEIN; GAMMA SECRETASE INHIBITOR; LY 411575; N2 [2 (3,5 DIFLUOROPHENYL) 2 HYDROXYETHANOYL] N1 (5 METHYL 6 OXO 6,7 DIHYDRO 5H DIBENZO[B,D]AZEPIN 7 YL)ALANINAMIDE; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN TISSUE; CENTRAL NERVOUS SYSTEM; CEREBROSPINAL FLUID; CONTROLLED STUDY; DRUG EFFICACY; ENZYME INHIBITION; FEMALE; HISTOPATHOLOGY; MALE; MEASUREMENT; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; QUANTITATIVE ANALYSIS; TRANSGENIC MOUSE;

ALANINE; AMYLOID BETA-PROTEIN; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; ASPARTIC ENDOPEPTIDASES; AZEPINES; BRAIN; DOSE-RESPONSE RELATIONSHIP, DRUG; ENDOPEPTIDASES; FEMALE; HUMANS; MALE; MICE; MICE, TRANSGENIC; PEPTIDE FRAGMENTS; PROTEASE INHIBITORS; RATS; RATS, SPRAGUE-DAWLEY;

EID: 20944432999     PISSN: 00223565     EISSN: None     Source Type: Journal    
DOI: 10.1124/jpet.104.081174     Document Type: Article

References (41)

1. Audia JE, Hyslop PA, Nissen JS, Thompson RC, Tung JS, and Tanner LL (2000) inventors, Elan Pharmaceuticals, Inc. and Eli Lilly and Company, assignees. Determining the mechanism of beta-amyloid peptide generation. U.S. patent WO 00/191210. 2000 Apr 6.
2. Baudoin O, Cesario M, Guenard D, and Gueritte F (2002) Application of the palladium-catalyzed borylation/Suzuki coupling (BSC) reaction to the synthesis of biologically active biaryl lactams. J Org Chem 67:1199-1207.
3. Carro E, Trejo JL, Gomez-Isla T, LeRoith D, and Torres-Aleman I (2002) Serum insulin-like growth factor I regulates brain amyloid-beta levels. Nat Med 8:1390-1397.
4. Chishti MA, Yang D-S, Janus C, Phinney AL, Horne P, Pearson J, Strome R, Zuker N, Loukides J, French J, et al. (2001) Early-onset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695. J Biol Chem 276:21562-21570.
5. Chromy BA, Nowak RJ, Lambert MP, Viola KL, Chang L, Velasco PT, Jones BW, Fernandez SJ, Lacor PN, Horowitz P, et al. (2003) Self-assembly of Abeta(1-42) into globular neurotoxins. Biochemistry 42:12749-12760.
6. Deane R, Wu Z, Sagare A, Davis J, Du Yan S, Hamm K, Xu F, Parisi M, LaRue B, Hu HW, et al. (2004) LRP/amyloid beta-peptide interaction mediates differential brain efflux of Abeta isoforms. Neuron 43:333-344.
7. DeMattos RB, Bales KR, Parsadanian M, O'Dell MA, Foss EM, Paul SM, and Holtzman DM (2002) Plaque-associated disruption of CSF and plasma amyloid-beta (Aβ) equilibrium in a mouse model of Alzheimer's disease. J Neurochem 81:229-236.
8. Dovey HF, John V, Anderson JP, Chen LZ, de Saint Andrieu P, Fang LY, Freedman SB, Folmer B, Goldbach E, Holsztynska EJ, et al. (2001) Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain. J Neurochem 76:173-181.
9. Games D, Adams D, Alessandrini R, Barbour R, Berthelette P, Blackwell C, Carr T, Clemens J, Donaldson T, Gillespie F, et al. (1995) Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein. Nature (Lond) 373:523-527.
10. Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L, et al. (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature (Lond) 349:704-706.
11. Haass C (2004) Take five-BACE and the γ-secretase quartet conduct Alzheimer's amyloid β-peptide generation. EMBO (Eur Mol Biol Organ) J 23:483-488.
12. Hardy J (1997) The Alzheimer family of diseases: many etiologies, one pathogenesis? Proc Natl Acad Sci USA 94:2095-2097.
13. Hardy J and Selkoe DJ (2002) The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science (Wash DC) 297:353-356. Erratum in: Science (Wash DC) 297:2209.
14. Hardy J and Selkoe DJ (2002) The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science (Wash DC) 297:353-356. Erratum in: Science (Wash DC) 297:2209.
15. Harrison DC, Irving EA, Buck T, Hussain I, Riddell D, Soden P, Dingwall C, Davis J, Parsons AA, and Hille C (2004a) Characterisation of the efficacy of the gamma secretase inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S- phenylglycine t-butyl ester (DAPT) in guinea pigs and in mice expressing the London or Swedish mutations. Soc Neurosci Abstr 675:7.
16. Harrison T, Churcher I, and Beher D (2004b) Gamma-secretase as a target for drug intervention in Alzheimer's disease. Curr Opin Drug Dis Dev 7:709-719.
17. Hartley DM, Walsh DM, Ye CP, Diehl T, Vasquez S, Vassilev PM, Teplow DB, and Selkoe DJ (1999) Protofibrillar intermediates of amyloid beta-protein induce acute electrophysiological changes and progressive neurotoxicity in cortical neurons. J Neurosci 19:8876-8878.
18. Hsia AY, Masliah E, McConlogue L, Yu GQ, Tatsuno G, Hu K, Kholodenko D, Malenka RC, Nicoll RA, and Mucke L (1999) Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models. Proc Natl Acad Sci USA 96:3228-3233.
19. Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, Yang F, and Cole G (1996) Correlative memory deficits, Abeta elevation and amyloid plaques in transgenic mice. Science (Wash DC) 274:99-102.
20. Ida N, Hartmann T, Pantel J, Schroder J, Zerfass R, Forstl H, Sandbrink R, Masters CL, and Beyreuther K (1996) Analysis of heterogeneous A4 peptides in human cerebrospinal fluid and blood by a newly developed sensitive Western blot assay. J Biol Chem 271:22908-22914.
21. Kawarabayashi T, Younkin LH, Saido TC, Shoji M, Ashe KH, and Younkin SG (2001) Age-dependent changes in brain, CSF and plasma amyloid (beta) protein in the Tg2576 transgenic mouse model of Alzheimer's disease. J Neurosci 21:372-381.
22. Kim KS, Miller DL, Sapienza VJ, Chen C-MJ, Bai C, Grundke-Iqbal I, Currie JR, and Wisniewski HM (1988) Production and characterization of monoclonal antibodies reactive to synthetic cerebrovascular amyloid peptide. Neurosci Res Commun 2:121-130.
23. Lambert MP, Barlow AK, Chromy BA, Edwards C, Freed R, Liosatos M, Morgan TE, Rozovsky I, Trommer B, Viola KL, et al. (1998) Diffusible, nonfibrillar ligands derived from Abeta 1-42 are potent central nervous system neurotoxins. Proc Natl Acad Sci USA 95:6448-6453.
24. Lanz TA, Himes CS, Pallante G, Adams L, Yamazaki S, Amore B, and Merchant KM (2003) The gamma-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl] -S-phenylglycine t-butyl ester reduces Abeta levels in vivo in plasma and cerebrospinal fluid in young (plaque-free) and aged (plaque-bearing) Tg2576 mice. J Pharmacol Exp Ther 305:864-871.
25. Lanz TA, Hosley JD, Adams WJ, and Merchant KM (2004) Studies of Aβ pharmacodynamics in the brain, cerebrospinal fluid and plasma in young (plaque-free) Tg2576 mice using the gamma-secretase inhibitor N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6-oxo-6, 7-dihydro-5Hdibenzo[b,d]azepin-7-yl)-L-alaninamide (LY-411575). J Pharmacol Exp Ther 309:49-55.
26. Lewis HD, Beher D, Smith D, Hewson L, Cookson N, Reynolds DS, Dawson GR, Jiang M, Van der Ploeg LH, Qian S, et al. (2004) Novel aspects of accumulation dynamics and A beta composition in transgenic models of AD. Neurobiol Aging 25:1175-1185.
27. Maruyama M, Arai H, Sugita M, Tanji H, Higuchi M, Okamura N, Matsui T, Higuchi S, Matsushita S, Yoshida H, and Sasaki H (2001) Cerebrospinal fluid amyloid beta(1-42) levels in the mild cognitive impairment stage of Alzheimer's disease. Exp Neurol 172:433-436.
28. Mehta PD, Pirttila T, Mehta SP, Sersen EA, Aisen PS, and Wisniewski HM (2000) Plasma and cerebrospinal fluid levels of amyloid beta proteins 1-40 and 1-42 in Alzheimer's disease. Arch Neurol 57:100-105.
29. Middendorp O, Luthi U, Hausch F, and Barberis A (2004) Searching for the most effective screening system to identify cell-active inhibitors of beta-secretase. Biol Chem 385:481-485.
30. Naslund J, Haroutunian V, Mohs R, Davis KL, Davies P, Greengard P, and Buxbaum JD (2000) Correlation between elevated levels of amyloid beta-peptide in the brain and cognitive decline. J Am Med Assoc 283:1571-1577.
31. Savage MJ, Trusko SP, Howland DS, Pinsker LR, Mistretta S, Reaume AG, Greenberg BD, Siman R, and Scott RW (1998) Turnover of amyloid beta-protein in mouse brain and acute reduction of its level by phorbol ester. J Neurosci 18:1743-1752.
32. Searfoss GH, Jordan WH, Calligaro DO, Galbreath EJ, Schirtzinger LM, Berridge BR, Gao H, Higgins MA, May PC, and Ryan TP (2003) Adipsin, a biomarker of gastrointestinal toxicity mediated by a functional gamma-secretase inhibitor. J Biol Chem 278:46107-46116.
33. Selkoe DJ (2001) Alzheimer's disease: genes, proteins and therapy. Physiol Rev 81:741-766.
34. Selkoe DJ and Schenk D (2003) Alzheimer's disease: molecular understanding predicts amyloid-based therapeutics. Annu Rev Pharmacol Toxicol 43:545-584.
35. Shibata M, Yamada S, Kumar SR, Calero M, Bading J, Frangione B, Holtzman DM, Miller CA, Strickland DK, Ghiso J, and Zlokovic BV (2000) Clearance of Alzheimer's amyloid-β(1-40) peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier. J Clin Investig 106:1489-1499.
36. Shin RW, Ogino K, Kondo A, Saido TC, Trojanowski JQ, Kitamoto T, and Tateishi J (1997) Amyloid beta-protein (Abeta) 1-40 but not Abeta 1-42 contributes to the experimental formation of Alzheimer disease amyloid fibrils in rat brain. J Neurosci 17:8187-8193.
37. Tanzi RE, Moir RD, and Wagner SL (2004) Clearance of Alzheimer's Aβ peptide: the many roads to perdition. Neuron. 43:605-608.
38. Wang J, Dickson DW, Trojanowski JQ, and Lee VM (1999) The levels of soluble versus insoluble brain Abeta distinguish Alzheimer's disease from normal and pathologic aging. Exp Neurol 158:328-337.
39. Wong GT, Manfra D, Poulet FM, Zhang Q, Josien H, Bara T, Engstrom L, Pinzon-Ortiz M, Fine JS, Lee H-JJ, et al. (2004) Chronic treatment with the gamma secretase inhibitor LY-411,575 inhibits beta-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation. J Biol Chem 279:12876-12882.
40. Wu J, Tung JS, Thorsett ED, Pleiss MA, Nissen J, Neitz J, Latimer LH, John V, Freedman SB, Britton TC, et al. (1998) inventors, Athena Neurosciences, Inc. and Eli Lilly and Company, assignees. Cycloalkyl, lactam, lactone and related compounds, pharmaceutical compositions comprising same and methods for inhibiting beta-amyloid peptide release and/or its synthesis by use of such compounds. U.S. Patent WO 98/28268. 1998 Jul 2.
41. Zheng H, Jiang M, Trumbauer ME, Hopkins R, Sirinathsinghji DJ, Stevens KA, Conner MW, Slunt HH, Sisodia SS, Chen HY, and Van der Ploeg LH (1996) Mice deficient for the amyloid precursor protein gene. Ann NY Acad Sci 777:421-426.