A Noncompetitive BACE1 Inhibitor TAK-070 ameliorates aβ pathology and behavioral deficits in a mouse model of Alzheimer's disease

Journal of Neuroscience

Volumn 30, Issue 33, 2010, Pages 11157-11166

  Fukumoto, Hiroaki ^a   Takahashi, Hideki ^a   Tarui, Naoki ^a   Matsui, Junji ^a   Tomita, Taisuke ^b   Hirode, Mitsuhiro ^a   Sagayama, Masumi ^a   Maeda, Ryouta ^a   Kawamoto, Makiko ^a   Hirai, Kazuko ^a   Terauchi, Jun ^a   Sakura, Yasufumi ^a   Kakihana, Mitsuru ^a   Kato, Kaneyoshi ^a   Iwatsubo, Takeshi ^b,c   Miyamoto, Masaomi ^a  

^a TAKEDA PHARMACEUTICAL COMPANY LIMITED   (Japan)

^b UNIVERSITY OF TOKYO   (Japan)

^c UNIVERSITY OF TOKYO   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

6 [(1,1' BIPHENYL) 4 YLMETHOXY] 1,2,3,4 TETRAHYDRO N,N DIMETHYL 2 NAPHTHALENE ETHAN AMINE HYDROCHLORIDE MONOHYDRATE; AMYLOID BETA PROTEIN; BETA SECRETASE INHIBITOR; PROTEINASE; TAK 070; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BEHAVIOR DISORDER; CONTROLLED STUDY; DRUG EFFICACY; FEMALE; HUMAN; HUMAN CELL; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; TRANSGENIC MOUSE;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN; AMYLOID BETA-PROTEIN PRECURSOR; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; ASPARTIC ACID ENDOPEPTIDASES; BIPHENYL COMPOUNDS; BRAIN; CELL LINE, TUMOR; COGNITION DISORDERS; DISEASE MODELS, ANIMAL; ENZYME INHIBITORS; FEASIBILITY STUDIES; FEMALE; HUMANS; MALE; MAZE LEARNING; MICE; MICE, TRANSGENIC; NAPHTHALENES; RANDOM ALLOCATION; RECEPTORS, CELL SURFACE; RECOGNITION (PSYCHOLOGY); TREATMENT OUTCOME;

EID: 77955863408     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.2884-10.2010     Document Type: Article

References (43)

1. Asami-Odaka A, Ishibashi Y, Kikuchi T, Kitada C, Suzuki N (1995) Long amyloid β-protein secreted from wild-type human neuroblastoma IMR-32 cells. Biochemistry 34:10272-10278.
2. Chen Q, Nakajima A, Choi SH, Xiong X, Tang YP (2008) Loss of presenilin function causes Alzheimer's disease-like neurodegeneration in the mouse. J Neurosci Res 86:1615-1625.
3. Cleary JP, Walsh DM, Hofmeister JJ, Shankar GM, Kuskowski MA, Selkoe DJ, Ashe KH (2005) Natural oligomers of the amyloid-β protein specifically disrupt cognitive function. Nat Neurosci 8:79-84.
4. Cole SL, Vassar R (2008) BACE1 structure and function in health and Alzheimer's disease. Curr Alzheimer Res 5:100-120. (Pubitemid 351536336)
5. Doedens JR, Mahimkar RM, Black RA (2003) TACE/ADAM-17 enzymatic activity is increased in response to cellular stimulation. Biochem Biophys Res Commun 308:331-338.
6. Donoviel DB, Hadjantonakis AK, Ikeda M, Zheng H, Hyslop PS, Bernstein A (1999) Mice lacking both presenilin genes exhibit early embryonic patterning defects. Genes Dev 13:2801-2810.
7. Espeseth AS, Xu M, Huang Q, Coburn CA, Jones KLG, Ferrer M, Zuck PD, Strulovici B, Price EA, Wu G, Wolfe AL, Lineberger JE, Sardana M, Tugusheva K, Pietrak BL, Crouthamel M-C, Lai M-T, Dodson EC, Bazzo R, Shi X-P, et al. (2005) Compounds that bind APP and inhibit Aβ processing in vitro suggest a novel approach to Alzheimer disease therapeutics. J Biol Chem 280:17792-17797.
8. Fukumoto H, Tomita T, Matsunaga H, Ishibashi Y, Saido TC, Iwatsubo T (1999) Primary cultures of neuronal and non-neuronal rat brain cells secrete similar proportions of amyloid β peptides ending at Aβ40 and Aβ42. Neuroreport 10:2965-2969.
9. Fukumoto H, Rosene DL, Moss MB, Raju S, Hyman BT, Irizarry MC (2004) β-secretase activity increases with aging in human, monkey, and mouse brain. Am J Pathol 164:719-725. (Pubitemid 38364685)
10. Hu X, Hicks CW, He W, Wong P, Macklin WB, Trapp BD, Yan R (2006) Bace1 modulates myelination in the central and peripheral nervous system. Nat Neurosci 9:1520-1525.
11. Hussain I, Hawkins J, Harrison D, Hille C, Wayne G, Cutler L, Buck T, Walter D, Demont E, Howes C, Naylor A, Jeffrey P, Gonzalez MI, Dingwall C, Michel A, Redshaw S, Davis JB (2007) Oral administration of a potent and selective non-peptidic BACE-1 inhibitor decreases β-cleavage of amyloid precursor protein and amyloid-β production in vivo. J Neurochem 100:802-809.
12. Isacson O, Seo H, Lin L, Albeck D, Granholm AC (2002) Alzheimer's disease and Down's syndrome: roles of APP, trophic factors and ACh. Trends Neurosci 25:79-84. (Pubitemid 34123299)
13. Iwatsubo T, Odaka A, Suzuki N, Mizusawa H, Nukina N, Ihara Y (1994) Visualization of Aβ42(43) and Aβ40 in senile plaques with end-specific Aβ monoclonals: evidence that an initially deposited species is Aβ42 (43). Neuron 13:45-53.
14. Jacobsen JS, Wu CC, Redwine JM, Comery TA, Arias R, Bowlby M, Martone R, Morrison JH, Pangalos MN, Reinhart PH, Bloom FE (2006) Earlyonset behavioral and synaptic deficits in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A 103:5161-5166.
15. Jorissen E, Prox J, Bernreuther C, Weber S, Schwanbeck R, Serneels L, Snellinx A, Craessaerts K, Thathiah A, Tesseur I, Bartsch U, Weskamp G, Blobel CP, Glatzel M, De Strooper B, Saftig P (2010) The disintegrin/ metalloproteinase ADAM10 is essential for the establishment of the brain cortex. J Neurosci 30:4833-4844.
16. Lakshmana MK, Yoon IS, Chen E, Bianchi E, Koo EH, Kang DE (2009) Novel role of RanBP9 in BACE1 processing of amyloid precursor protein and amyloid β peptide generation. J Biol Chem 284:11863-11872.
17. Marks N, Berg MJ (2008) Neurosecretases provide strategies to treat sporadic and familial Alzheimer disorders. Neurochem Int 52:184-215. (Pubitemid 350235705)
18. Marlow L, Cain M, Pappolla MA, Sambamurti K (2003) β-Secretase processing of the Alzheimer's amyloid protein precursor (APP). J Mol Neurosci 20:233-239.
19. McConlogue L, Buttini M, Anderson JP, Brigham EF, Chen KS, Freedman SB, Games D, Johnson-Wood K, Lee M, Zeller M, Liu W, Motter R, Sinha S (2007) Partial reduction of BACE1 has dramatic effects on Alzheimer plaque and synaptic pathology in APP transgenic mice. J Biol Chem 282:26326-26334.
20. Obregon DF, Rezai-Zadeh K, Bai Y, Sun N, Hou H, Ehrhart J, Zeng J, Mori T, Arendash GW, Shytle D, Town T, Tan J (2006) ADAM10 activation is required for green tea (-)-epigallocatechin-3-gallate-induced (alpha)-secretase cleavage of amyloid precursor protein. J Biol Chem 281:16419-16427.
21. Ohno M, Sametsky EA, Younkin LH, Oakley H, Younkin SG, Citron M, Vassar R, Disterhoft JF (2004) BACE1 deficiency rescues memory deficits and cholinergic dysfunction in a mouse model of Alzheimer's disease. Neuron 41:27-33.
22. Ohno M, Chang L, Tseng W, Oakley H, Citron M, Klein WL, Vassar R, Disterhoft JF (2006) Temporal memory deficits in Alzheimer's mouse models: rescue by genetic deletion of BACE1. Eur J Neurosci 23:251-260.
23. Ohno M, Cole SL, Yasvoina M, Zhao J, Citron M, Berry R, Disterhoft JF, Vassar R (2007) BACE1 gene deletion prevents neuron loss and memory deficits in 5XFAD APP/PS1 transgenic mice. Neurobiol Dis 26:134-145.
24. Postina R (2008) A closer look at α-secretase. Curr Alzheimer Res 5:179-186.
25. Sankaranarayanan S, Price EA, WuG, Crouthamel MC, Shi XP, Tugusheva K, Tyler KX, Kahana J, Ellis J, Jin L, Steele T, Stachel S, Coburn C, Simon AJ (2008) In vivo beta-secretase 1 inhibition leads to brain Aβ lowering and increased α-secretase processing of amyloid precursor protein without effect on neuregulin-1. J Pharmacol Exp Ther 324:957-969.
26. Sankaranarayanan S, Holahan MA, Colussi D, Crouthamel MC, Devanarayan V, Ellis J, Espeseth A, Gates AT, Graham SL, Gregro AR, Hazuda D, Hochman JH, Holloway K, Jin L, Kahana J, Lai MT, Lineberger J, McGaughey G, Moore KP, Nantermet P, et al. (2009) First demonstration of cerebrospinal fluid and plasma Aβ lowering with oral administration of a β-site amyloid precursor protein-cleaving enzyme 1 inhibitor in nonhuman primates. J Pharmacol Exp Ther 328:131-140.
27. Saura CA, Choi SY, Beglopoulos V, Malkani S, Zhang D, Shankaranarayana Rao BS, Chattarji S, Kelleher RJ 3rd, Kandel ER, Duff K, Kirkwood A, Shen J (2004) Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration. Neuron 42:23-36.
28. 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.
29. Savonenko AV, Melnikova T, Laird FM, Stewart KA, Price DL, Wong PC (2008) Alteration of BACE1-dependent NRG1/ErbB4 signaling and schizophrenia-like phenotypes in BACE1-null mice. Proc Natl Acad Sci U S A 105:5585-5590. (Pubitemid 351753906)
30. Selkoe DJ, Schenk D (2003) Alzheimer's disease: molecular understanding predicts amyloid-based therapeutics. Annu Rev Pharmacol Toxicol 43:545-584.
31. Shen J, Bronson RT, Chen DF, Xia W, Selkoe DJ, Tonegawa S (1997) Skeletal and CNS defects in Presenilin-1-deficient mice. Cell 89:629-639. (Pubitemid 27511773)
32. Silvestri R (2009) Boom in the development of non-peptidic β-secretase (BACE1) inhibitors for the treatment of Alzheimer's disease. Med Res Rev 29:295-338.
33. 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 β-secretase from human brain. Nature 402:537-540.
34. Stockley JH, O'Neill C (2007) The proteins BACE1 and BACE2 and β-secretase activity in normal and Alzheimer's disease brain. Biochem Soc Trans 35:574-576.
35. Takahashi Y, Hayashi I, Tominari Y, Rikimaru K, Morohashi Y, Kan T, Natsugari H, Fukuyama T, Tomita T, Iwatsubo T (2003) Sulindac sulfide is a noncompetitive γ-secretase inhibitor that preferentially reduces Aβ42 generation. J Biol Chem 278:18664-18670. (Pubitemid 36799494)
36. Tomita T, Katayama R, Takikawa R, Iwatsubo T (2002) Complex N-glycosylated form of nicastrin is stabilized and selectively bound to presenilin fragments. FEBS Lett 520:117-121.
37. 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) β-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286:735-741.
38. Venkitaramani DV, Chin J, Netzer WJ, Gouras GK, Lesne S, Malinow R, Lombroso PJ (2007) β-Amyloid modulation of synaptic transmission and plasticity. J Neurosci 27:11832-11837. (Pubitemid 350072092)
39. Walsh DM, Klyubin I, Fadeeva JV, Cullen WK, Anwyl R, Wolfe MS, Rowan MJ, Selkoe DJ (2002) Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416:535-539. (Pubitemid 34288854)
40. Westerman MA, Cooper-Blacketer D, Mariash A, Kotilinek L, Kawarabayashi T, Younkin LH, Carlson GA, Younkin SG, Ashe KH (2002) The relationship between Aβ and memory in the Tg2576 mouse model of Alzheimer's disease. J Neurosci 22:1858-1867.
41. Westmeyer GG, Willem M, Lichtenthaler SF, Lurman G, Multhaup G, Assfalg-Machleidt I, Reiss K, Saftig P, Haass C (2004) Dimerization of β-site β-amyloid precursor protein-cleaving enzyme. J Biol Chem 279: 53205-53212. (Pubitemid 40051823)
42. Wong PC, Zheng H, Chen H, Becher MW, Sirinathsinghji DJ, Trumbauer ME, Chen HY, Price DL, Van der Ploeg LH, Sisodia SS (1997) Presenilin 1 is required for Notch1 and DII1 expression in the paraxial mesoderm. Nature 387:288-292.
43. Zohar O, Pick CG, Cavallaro S, Chapman J, Katzav A, Milman A, Alkon DL (2005) Age-dependent differential expression of BACE splice variants in brain regions of tg2576 mice. Neurobiol Aging 26:1167-1175. (Pubitemid 40726009)