Differential effects between γ-Secretase inhibitors and modulators on cognitive function in amyloid precursor protein-transgenic and nontransgenic mice

Journal of Neuroscience

Volumn 32, Issue 6, 2012, Pages 2037-2050

  Mitani, Yasuyuki ^a   Yarimizu, Junko ^a   Saita, Kyoko ^a   Uchino, Hiroshi ^a   Akashiba, Hiroki ^a   Shitaka, Yoshitsugu ^a   Ni, Keni ^a   Matsuoka, Nobuya ^a  

^a ASTELLAS PHARMA INC   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

[[(2S 4R) 1 [(4R) 1 1 1 TRIFLUORO 7 METHYLOCTAN 4 YL] 2 [4 (TRIFLUOROMETHYL)PHENYL]PIPERIDIN 4 YL]ACETIC ACID; AMYLOID BETA PROTEIN; AMYLOID BETA PROTEIN 38; AMYLOID BETA PROTEIN [1-40]; AMYLOID BETA PROTEIN [1-42]; AMYLOID PRECURSOR PROTEIN; AVAGACESTAT; CENTRAL NERVOUS SYSTEM AGENTS; EPHRIN RECEPTOR A4; GAMMA SECRETASE; GAMMA SECRETASE INHIBITOR; GAMMA SECRETASE MODULATOR; NERVE CELL ADHESION MOLECULE; NOTCH RECEPTOR; PIPERIDINE DERIVATIVE; SEMAGACESTAT; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CARBOXY TERMINAL SEQUENCE; COGNITION; COMPARATIVE STUDY; CONTROLLED STUDY; DENTATE HILUS; DRUG EFFECT; DRUG MEGADOSE; FEMALE; GENE EXPRESSION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HIPPOCAMPAL STRATUM LUCIDUM; HUMAN; HUMAN CELL; IMMUNOFLUORESCENCE; MALE; MASS SPECTROMETRY; MAZE TEST; MOUSE; NERVE ENDING; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN DETERMINATION; PROTEIN LOCALIZATION; SIGNAL TRANSDUCTION; SPATIAL MEMORY; TRANSGENIC MOUSE; WESTERN BLOTTING;

ALANINE; AMYLOID BETA-PROTEIN PRECURSOR; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; AZEPINES; CELL LINE, TUMOR; COGNITION; FEMALE; HUMANS; MAZE LEARNING; MICE; MICE, TRANSGENIC; PROTEASE INHIBITORS;

EID: 84857020179     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.4264-11.2012     Document Type: Article

References (70)

1. Alberi L, Liu S, Wang Y, Badie R, Smith-Hicks C, WuJ, Pierfelice TJ, Abazyan B, Mattson MP, Kuhl D, Pletnikov M, Worley PF, Gaiano N (2011) Activity-induced Notch signaling in neurons requires Arc/Arg3.1 and is essential for synaptic plasticity in hippocampal networks. Neuron 69:437-444.
2. Allison JG, Das PM, Ma J, Inglis FM, Jones FE (2011) The ERBB4 intracellular domain (4ICD) regulates NRG1-induced gene expression in hippocampal neurons. Neurosci Res 70:155-163.
3. Beher D, Wrigley JD, Owens AP, Shearman MS (2002) Generation of C-terminally truncated amyloid-beta peptides is dependent on gammasecretase activity. J Neurochem 82:563-575.
4. Bittner T, FuhrmannM, Burgold S, Jung CK, Volbracht C, Steiner H, Mitteregger G, Kretzschmar HA, Haass C, Herms J (2009) α-Secretase inhibition reduces spine density in vivo via an amyloid precursor protein-dependent pathway. J Neurosci 29:10405-10409.
5. Bot N, Schweizer C, Ben Halima S, Fraering PC (2011) Processing of the synaptic cell adhesion molecule Neurexin-3+ by Alzheimer diseaseβ-and α-secretases. J Biol Chem 286:2762-2773.
6. Cirrito JR, May PC, O'Dell MA, Taylor JW, Parsadanian M, Cramer JW, Audia JE, Nissen JS, Bales KR, Paul SM, DeMattos RB, Holtzman DM (2003) In vivo assessment of brain interstitial fluid with microdialysis reveals plaque-associated changes in amyloid-α metabolism and half-life. J Neurosci 23:8844-8853.
7. Cirrito JR, Yamada KA, Finn MB, Sloviter RS, Bales KR, May PC, Schoepp DD, Paul SM, Mennerick S, HoltzmanDM (2005) Synaptic activity regulates interstitial fluid amyloid-beta levels in vivo. Neuron 48:913-922.
8. Comery TA, Martone RL, Aschmies S, Atchison KP, Diamantidis G, Gong X, Zhou H, Kreft AF, Pangalos MN, Sonnenberg-Reines J, Jacobsen JS, Marquis KL (2005) Acute α-secretase inhibition improves contextual fear conditioning in the Tg2576 mouse model of Alzheimer's disease. J Neurosci 25:8898-8902.
9. Cook JJ, Wildsmith KR, Gilberto DB, Holahan MA, Kinney GG, Mathers PD, Michener MS, Price EA, Shearman MS, Simon AJ, Wang JX, Wu G, Yarasheski KE, Bateman RJ (2010) Acute α-secretase inhibition of nonhuman primate CNS shifts amyloid precursor protein (APP) metabolism from amyloid-α production to alternative APP fragments without amyloid-α rebound. J Neurosci 30:6743-6750.
10. Costa RM, Honjo T, Silva AJ (2003) Learning and memory deficits in Notch mutant mice. Curr Biol 13:1348-1354.
11. De Strooper B, Saftig P, Craessaerts K, Vanderstichele H, Guhde G, Annaert W, Von Figura K, Van Leuven F (1998) Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature 391:387-390.
12. De Strooper B, Annaert W, Cupers P, Saftig P, Craessaerts K, Mumm JS, Schroeter EH, Schrijvers V, Wolfe MS, Ray WJ, Goate A, Kopan R (1999) A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature 398:518-522.
13. Dewachter I, Reversé D, Caluwaerts N, Ris L, Kuipéri C, Van den Haute C, Spittaels K, Umans L, Serneels L, Thiry E, Moechars D, Mercken M, Godaux E, Van Leuven F (2002) Neuronal deficiency of presenilin 1 inhibits amyloid plaque formation and corrects hippocampal long-term potentiation but not a cognitive defect of amyloid precursor protein [V717I] transgenic mice. J Neurosci 22:3445-3453.
14. Eriksen JL, Sagi SA, Smith TE, Weggen S, Das P, McLendon DC, Ozols VV, Jessing KW, Zavitz KH, Koo EH, Golde TE (2003) NSAIDs and enantiomers of flurbiprofen target gamma-secretase and lower Abeta 42 in vivo. J Clin Invest 112:440-449.
15. Fleisher AS, Raman R, Siemers ER, Becerra L, Clark CM, Dean RA, Farlow MR, Galvin JE, Peskind ER, Quinn JF, Sherzai A, Sowell BB, Aisen PS, Thal LJ (2008) Phase 2 safety trial targeting amyloid beta production with a gamma-secretase inhibitor in Alzheimer disease. Arch Neurol 65:1031-1038.
16. Gillman KW, Starrett JE, Parker MF, Xie K, Bronson JJ, Marcin LR, McElhone KE, Bergstrom CP, Mate RA, Williams R, Meredith JE, Burton CR, Barten DM, Toyn JH, Roberts SB, Lentz KA, Houston JG, Zaczek R, Albright CF, Decicco CP, et al. (2010) Discovery and evaluation of BMS-708163, a potent, selective and orally bioavailable α-secretase inhibitor. ACS Med Chem Lett 1:120-124.
17. Henley DB, May PC, Dean RA, Siemers ER (2009) Development of semagacestat (LY450139), a functionalβ-secretase inhibitor, for the treatment of Alzheimer's disease. Expert Opin Pharmacother 10:1657-1664.
18. Holcomb LA, Gordon MN, Jantzen P, Hsiao K, Duff K, Morgan D (1999) Behavioral changes in transgenic mice expressing both amyloid precursor protein and presenilin-1 mutations: lack of association with amyloid deposits. Behav Genet 29:177-185.
19. Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, Yang F, Cole G (1996) Correlative memory deficits, Aβ elevation, and amyloid plaques in transgenic mice. Science 274:99-102.
20. Imbimbo BP, Hutter-Paier B, Villetti G, Facchinetti F, Cenacchi V, Volta R, Lanzillotta A, Pizzi M, Windisch M (2009) CHF5074, a novel α-secretase modulator, attenuates brain α-amyloid pathology and learning deficit in a mouse model of Alzheimer's disease. Br J Pharmacol 156:982-993.
21. Inoue E, Deguchi-Tawarada M, Togawa A, Matsui C, Arita K, Katahira-Tayama S, Sato T, Yamauchi E, Oda Y, Takai Y (2009) Synaptic activity prompts gamma-secretase-mediated cleavage of EphA4 and dendritic spine formation. J Cell Biol 185:551-564.
22. Iwatsubo T, Odaka A, Suzuki N, Mizusawa H, Nukina N, Ihara Y (1994) Visualization of A beta 42(43) and A beta 40 in senile plaques with endspecific A beta monoclonals: evidence that an initially deposited species is A beta 42(43). Neuron 13:45-53.
23. Jarrett JT, Berger EP, Lansbury PT Jr (1993) The carboxy terminus of the beta amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheimer's disease. Biochemistry 32:4693-4697.
24. Jiang Y, Mullaney KA, PeterhoffCM, Che S, Schmidt SD, Boyer-Boiteau A, Ginsberg SD, Cataldo AM, Mathews PM, Nixon RA (2010) Alzheimer's-related endosome dysfunction in Down syndrome is Abeta-independent but requires APP and is reversed by BACE-1 inhibition. Proc Natl Acad Sci U S A 107:1630-1635.
25. Jinno S, Araki K, Matsumoto Y, Suh YH, Yamamoto T (2009) Selective apoptosis induction in the hippocampal mossy fiber pathway by exposure to CT105, the C-terminal fragment of Alzheimer's amyloid precursor protein. Brain Res 1249:68-78.
26. Kamenetz F, Tomita T, Hsieh H, Seabrook G, Borchelt D, Iwatsubo T, Sisodia S, Malinow R (2003) APP processing and synaptic function. Neuron 37:925-937.
27. Kawarabayashi T, Shoji M, Younkin LH, Wen-Lang L, Dickson DW, Murakami T, Matsubara E, Abe K, Ashe KH, Younkin SG (2004) Dimeric amyloid α protein rapidly accumulates in lipid rafts followed by apolipoprotein E and phosphorylated tau accumulation in the Tg2576 mouse model of Alzheimer's disease. J Neurosci 24:3801-3809.
28. Kim HJ, Suh YH, Lee MH, Ryu PD (1999) Cation selective channels formed by a C-terminal fragment of beta-amyloid precursor protein. Neuroreport 10:1427-1431.
29. Kim SH, Suh YH (1996) Neurotoxicity of a carboxyl-terminal fragment of the Alzheimer's amyloid precursor protein. J Neurochem 67:1172-1182.
30. Kopan R, Ilagan MX (2004) Gamma-secretase: proteasome of the membrane? Nat Rev Mol Cell Biol 5:499-504.
31. Kopan R, Schroeter EH, Weintraub H, Nye JS (1996) Signal transduction by activated mNotch: importance of proteolytic processing and its regulation by the extracellular domain. Proc Natl Acad Sci U S A 93:1683-1688.
32. Kounnas MZ, Danks AM, Cheng S, Tyree C, Ackerman E, Zhang X, Ahn K, Nguyen P, Comer D, Mao L, Yu C, Pleynet D, Digregorio PJ, Velicelebi G, Stauderman KA, Comer WT, Mobley WC, Li YM, Sisodia SS, Tanzi RE, et al. (2010) Modulation of α-secretase reduces α-amyloid deposition in a transgenic mouse model of Alzheimer's disease. Neuron 67:769-780.
33. Kreft AF, Martone R, Porte A (2009) Recent advances in the identification of α-secretase inhibitors to clinically test the Aβ oligomer hypothesis of Alzheimer's disease. J Med Chem 52:6169-6188.
34. Kukar T, Prescott S, Eriksen JL, Holloway V, Murphy MP, Koo EH, Golde TE, Nicolle MM (2007) Chronic administration of R-flurbiprofen attenuates learning impairments in transgenic amyloid precursor protein mice. BMC Neurosci 8:54.
35. Kuperstein I, Broersen K, Benilova I, Rozenski J, Jonckheere W, Debulpaep M, Vandersteen A, Segers-Nolten I, Van Der Werf K, Subramaniam V, Braeken D, Callewaert G, Bartic C, D'Hooge R, Martins IC, Rousseau F, Schymkowitz J, De Strooper B (2010) Neurotoxicity of Alzheimer's disease Abeta peptides is induced by small changes in the Abeta42 to Abeta40 ratio. EMBO J 29:3408-3420.
36. Lacor PN, Buniel MC, Furlow PW, Clemente AS, Velasco PT, Wood M, Viola KL, KleinWL (2007) Aβ oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer's disease. J Neurosci 27:796-807.
37. Laird FM, Cai H, Savonenko AV, Farah MH, He K, Melnikova T, Wen H, Chiang HC, Xu G, Koliatsos VE, Borchelt DR, Price DL, Lee HK, Wong PC (2005) BACE1, a major determinant of selective vulnerability of the brain to amyloid-β amyloidogenesis, is essential for cognitive, emotional, and synaptic functions. J Neurosci 25:11693-11709.
38. Lee MK, Slunt HH, Martin LJ, Thinakaran G, Kim G, Gandy SE, Seeger M, Koo E, Price DL, Sisodia SS (1996) Expression of presenilin 1 and 2 (PS1 and PS2) in human and murine tissues. J Neurosci 16:7513-7525.
39. Lue LF, Kuo YM, Roher AE, Brachova L, Shen Y, Sue L, Beach T, Kurth JH, Rydel RE, Rogers J (1999) Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer's disease. Am J Pathol 155:853-862.
40. Marambaud P, Wen PH, Dutt A, Shioi J, Takashima A, Siman R, Robakis NK (2003) A CBP binding transcriptional repressor produced by the PS1/epsilon-cleavage of N-cadherin is inhibited by PS1 FAD mutations. Cell 114:635-645.
41. Martone RL, Zhou H, Atchison K, Comery T, Xu JZ, Huang X, Gong X, Jin M, Kreft A, Harrison B, Mayer SC, Aschmies S, Gonzales C, Zaleska MM, Riddell DR, Wagner E, Lu P, Sun SC, Sonnenberg-Reines J, Oganesian A, 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.
42. McCarthy JV, Twomey C, Wujek P (2009) Presenilin-dependent regulated intramembrane proteolysis and gamma-secretase activity. Cell Mol Life Sci 66:1534-1555.
43. McGowan E, Pickford F, Kim J, Onstead L, Eriksen J, Yu C, Skipper L, Murphy MP, Beard J, Das P, Jansen K, Delucia M, Lin WL, Dolios G, Wang R, Eckman CB, Dickson DW, Hutton M, Hardy J, Golde T (2005) Abeta42 is essential for parenchymal and vascular amyloid deposition in mice. Neuron 47:191-199.
44. McLean CA, Cherny RA, Fraser FW, Fuller SJ, Smith MJ, Beyreuther K, Bush AI, Masters CL (1999) Soluble pool of Abeta amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease. Ann Neurol 46:860-866.
45. Milano J, McKay J, Dagenais C, Foster-Brown L, Pognan F, Gadient R, Jacobs RT, Zacco A, Greenberg B, Ciaccio PJ (2004) Modulation of Notch processing by α-secretase inhibitors causes intestinal goblet cell metaplasia and induction of genes known to specify gut secretory lineage differentiation. Toxicol Sci 82:341-358.
46. Mucke L, Masliah E, Yu GQ, Mallory M, Rockenstein EM, Tatsuno G, Hu K, Kholodenko D, Johnson-Wood K, McConlogue L (2000) High-level neuronal expression of Aβ 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J Neurosci 20:4050-4058.
47. Nalbantoglu J, Tirado-Santiago G, Lahsaïni A, Poirier J, Goncalves O, Verge G, Momoli F, Welner SA, Massicotte G, Julien JP, Shapiro ML (1997) Impaired learning and LTP in mice expressing the carboxy terminus of the Alzheimer amyloid precursor protein. Nature 387:500-505.
48. Oehlrich D, Berthelot DJC, Gijsen HJ (2011) α-Secretase modulators as potential disease modifying anti-Alzheimer's drugs. J Med Chem 54:669-698.
49. Oster-Granite ML, McPhie DL, Greenan J, Neve RL (1996) Age-dependent neuronal and synaptic degeneration in mice transgenic for theCterminus of the amyloid precursor protein. J Neurosci 16:6732-6741.
50. Palop JJ, Mucke L, Roberson ED (2011) Quantifying biomarkers of cognitive dysfunction and neuronal network hyperexcitability in mouse models of Alzheimer's disease: depletion of calcium-dependent proteins and inhibitory hippocampal remodeling. Methods Mol Biol 670:245-262.
51. Portelius E, Price E, Brinkmalm G, Stiteler M, Olsson M, Persson R, Westman-Brinkmalm A, Zetterberg H, Simon AJ, Blennow K (2011) A novel pathway for amyloid precursor protein processing. Neurobiol Aging 32:1090-1098.
52. Pu YJ, Vaid RK, Boini SK, Towsley RW, Doecke CW, Mitchell D (2008) A practical method for functionalized peptide or amide bond formation in aqueous-ethanol media with EDC as activator. Org Process Res Dev 13:310-314.
53. Rushworth JV, Hooper NM (2010) Lipid rafts: linking Alzheimer's amyloid-beta production, aggregation, and toxicity at neuronal membranes. Int J Alzheimers Dis 2011:603052.
54. Saura CA, Chen G, Malkani S, Choi SY, Takahashi RH, Zhang D, Gouras GK, Kirkwood A, Morris RG, Shen J (2005) Conditional inactivation of presenilin 1 prevents amyloid accumulation and temporarily rescues contextual and spatial working memory impairments in amyloid precursor protein transgenic mice. J Neurosci 25:6755-6764.
55. Siemers E, Henley D, Sundell K, Sethuraman G, Dean R, Wrobleski K, Mohs R (2011) Evaluating semagacestat, a gamma-secretase inhibitor, in a phase III trial. Alzheimers Dement 7:S484-S485.
56. Sinha S, Anderson JP, Barbour R, Basi GS, Caccavello R, Davis D, Doan M, Dovey HF, Frigon N, Hong J, Jacobson-Croak K, Jewett N, Keim P, Knops J, Lieberburg I, Power M, Tan H, Tatsuno G, Tung J, Schenk D, et al. (1999) Purification and cloning of amyloid precursor protein betasecretase from human brain. Nature 402:537-540.
57. Struhl G, Greenwald I (1999) Presenilin is required for activity and nuclear access of Notch in Drosophila. Nature 398:522-525.
58. Suh YH, Kim HS, Lee JP, Park CH, Jeong SJ, Kim SS, Rah JC, Seo JH, Kim SS (2000) Roles of A beta and carboxyl terminal peptide fragments of amyloid precursor protein in Alzheimer disease. J Neural Transm Suppl 2000:65-82.
59. Townsend M, QuY, Gray A, WuZ, Seto T, Hutton M, Shearman MS, Middleton RE (2010) Oral treatment with a gamma-secretase inhibitor improves long-term potentiation in a mouse model of Alzheimer's disease. J Pharmacol Exp Ther 333:110-119.
60. Van Dam D, D'Hooge R, Staufenbiel M, Van Ginneken C, Van Meir F, De Deyn PP (2003) Age-dependent cognitive decline in the APP23 model precedes amyloid deposition. Eur J Neurosci 17:388-396.
61. Vassar R, Bennett BD, Babu-Khan S, Kahn S, Mendiaz EA, Denis P, Teplow DB, Ross S, Amarante P, Loeloff R, Luo Y, Fisher S, Fuller J, Edenson S, Lile J, Jarosinski MA, Biere AL, Curran E, Burgess T, Louis JC, et al. (1999) Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286:735-741.
62. Wang Y, Chan SL, Miele L, Yao PJ, Mackes J, Ingram DK, Mattson MP, Furukawa K (2004) Involvement of Notch signaling in hippocampal synaptic plasticity. Proc Natl Acad Sci U S A 101:9458-9462.
63. Weggen S, Eriksen JL, Das P, Sagi SA, Wang R, Pietrzik CU, Findlay KA, Smith TE, Murphy MP, Bulter T, Kang DE, Marquez-Sterling N, Golde TE, Koo EH (2001) A subset of NSAIDs lower amyloidogenic Aβ42 independently of cyclooxygenase activity. Nature 414:212-216.
64. Weggen S, Eriksen JL, Sagi SA, Pietrzik CU, Golde TE, Koo EH (2003) Aβ42-lowering nonsteroidal anti-inflammatory drugs preserve intramembrane cleavage of the amyloid precursor protein (APP) and ErbB-4 receptor and signaling through the APP intracellular domain. J Biol Chem 278:30748-30754.
65. Wei W, Nguyen LN, Kessels HW, Hagiwara H, Sisodia S, Malinow R (2010) Amyloid beta from axons and dendrites reduces local spine number and plasticity. Nat Neurosci 13:190-196.
66. Wolfe MS, Xia W, Ostaszewski BL, Diehl TS, Kimberly WT, Selkoe DJ (1999) Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and α-secretase activity. Nature 398:513-517.
67. Wong GT, Manfra D, Poulet FM, Zhang Q, Josien H, Bara T, Engstrom L, Pinzon-Ortiz M, Fine JS, Lee HJ, Zhang L, Higgins GA, Parker EM (2004) Chronic treatment with the α-secretase inhibitor LY-411,575 inhibits α-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation. J Biol Chem 279:12876-12882.
68. Yan R, Bienkowski MJ, Shuck ME, Miao H, Tory MC, Pauley AM, Brashier JR, Stratman NC, Mathews WR, Buhl AE, Carter DB, Tomasselli AG, Parodi LA, Heinrikson RL, GurneyME (1999) Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity. Nature 402:533-537.
69. Yan XX, Li T, Rominger CM, Prakash SR, Wong PC, Olson RE, Zaczek R, Li YW (2004) Binding sites of α-secretase inhibitors in rodent brain: distribution, postnatal development, and effect of deafferentation. J Neurosci 24:2942-2952.
70. Younkin SG (1998) The role of A beta 42 in Alzheimer's disease. J Physiol Paris 92:289-292.