BACE2, as a novel APP θ-secretase, is not responsible for the pathogenesis of Alzheimer's disease in Down syndrome

FASEB Journal

Volumn 20, Issue 9, 2006, Pages 1369-1376

  Sun, Xiulian ^a,b   He, Guiqiong ^a,c   Song, Weihong ^a,b  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^b UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^c CHONGQING MEDICAL UNIVERSITY   (China)

Author keywords

secretase; Alzheimer; BACE2; Down syndrome; Trisomy 21

Indexed keywords

AMYLOID BETA PROTEIN; BACE2 ENZYME; BETA SECRETASE; ASPARTIC PROTEINASE; BETA SITE APP CLEAVING ENZYME 2; BETA-SITE APP CLEAVING ENZYME 2; ENZYME INHIBITOR; RECOMBINANT PROTEIN; SECRETASE;

ALZHEIMER DISEASE; AMINO ACID SEQUENCE; ANIMAL CELL; ARTICLE; BINDING SITE; BRAIN NERVE CELL; CONTROLLED STUDY; DOWN SYNDROME; GENE OVEREXPRESSION; GENETIC TRANSCRIPTION; LENTIVIRINAE; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN DEGRADATION; ANIMAL; CELL CULTURE; CELL LINE; DRUG ANTAGONISM; ENZYMOLOGY; GENE VECTOR; GENETIC TRANSFECTION; GENETICS; HUMAN; KIDNEY; METABOLISM; MOLECULAR CLONING; MOUSE; NERVE CELL; PATHOPHYSIOLOGY; PHYSIOLOGY; PLASMID; POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TRANSGENIC MOUSE;

LENTIVIRUS; MUS MUSCULUS;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; ASPARTIC ENDOPEPTIDASES; CELL LINE; CELLS, CULTURED; CLONING, MOLECULAR; DOWN SYNDROME; ENZYME INHIBITORS; GENETIC VECTORS; HUMANS; KIDNEY; MICE; MICE, TRANSGENIC; NEURONS; PLASMIDS; POLYMERASE CHAIN REACTION; RECOMBINANT PROTEINS; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; TRANSCRIPTION, GENETIC; TRANSFECTION;

EID: 33746549926     PISSN: 08926638     EISSN: None     Source Type: Journal    
DOI: 10.1096/fj.05-5632com     Document Type: Article

References (66)

1. Down, J. L. H. (1866) Observations on an ethnic classification of idiots. London Hosp. Reports 3, 259-262
2. Jacobs, P. A., Baikie, A. G., Court Brown, W. M., and Strong, J. A. (1959) The somatic chromosomes in mongolism. Lancet 1, 710
3. Lejeune, J., Turpin, R., and Gautier, M. (1959) [Mongolism; a chromosomal disease (trisomy).]. Bull. Acad. Natl. Med. 143, 256-265
4. Glenner, G. G., and Wong, C. W. (1984) Alzheimer's disease and Down's syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem. Biophys. Res. Commun. 122, 1131-1135
5. Glenner, G. G., and Wong, C. W. (1984) Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem. Biophys. Res. Commun. 120, 885-890
6. Hardy, J., and Selkoe, D. J. (2002) The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297, 353-356
7. Cai, H., Wang, Y., McCarthy, D., Wen, H., Borchelt, D. R., Price, D. L., and Wong, P. C. (2001) BACE1 is the major beta-secretase for generation of Abeta peptides by neurons. Nat. Neurosci. 4, 233-234
8. Hussain, I., Powell, D., Howlett, D. R., Tew, D. G., Meek, T. D., Chapman, C., Gloger, I. S., Murphy, K. E., Southan, C. D., Ryan, D. M., et al. (1999) Identification of a novel aspartic protease (Asp 2) as beta-secretase. Mol. Cell Neurosci. 14, 419-427
9. Luo, Y., Bolon, B., Kahn, S., Bennett, B. D., Babu-Khan, S., Denis, P., Fan, W., Kha, H., Zhang, J., Gong, Y., et al. (2001) Mice deficient in BACE1, the Alzheimer's beta-secretase, have normal phenotype and abolished beta-amyloid generation. Nat. Neurosci. 4, 231-232
10. Roberds, S. L., Anderson, J., Basi, G., Bienkowski, M. J., Branstetter, D. G., Chen, K. S., Freedman, S. B., Frigon, N. L., Games, D., Hu, K., et al. (2001) BACE knockout mice are healthy despite lacking the primary beta-secretase activity in brain: implications for Alzheimer's disease therapeutics. Hum. Mol. Genet. 10, 1317-1324
11. Sinha, S., Anderson, J. P., Barbour, R., Basi, G. S., Caccavello, R., Davis, D., Doan, M., Dovey, H. F., Frigon, N., Hong, J., et al. (1999) Purification and cloning of amyloid precursor protein beta-secretase from human brain. Nature 402, 537-540
12. Vassar, R., Bennett, B. D., Babu-Khan, S., Kahn, S., Mendiaz, E. A., Denis, P., Teplow, D. B., Ross, S., Amarante, P., Loeloff, R., et al. (1999) Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286, 735-741
13. Yan, R., Bienkowski, M. J., Shuck, M. E., Miao, H., Tory, M. C., Pauley, A. M., Brashier, J. R., Stratman, N. C., Mathews, W. R., Buhl, A. E., et al. (1999) Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity. Nature 402, 533-537
14. Busciglio, J., Pelsman, A., Wong, C., Pigino, G., Yuan, M., Mori, H., and Yankner, B. A. (2002) Altered metabolism of the amyloid beta precursor protein is associated with mitochondrial dysfunction in Down's syndrome. Neuron 33, 677-688
15. Sun, X., Tong, Y., Qing, H., Chen, C., and Song, W. (2006) Increased BACE1 maturation contributes to Alzheimer's disease pathogenesis in Down syndrome. FASEB J. 20, 1361-1368
16. Acquati, F., Accarino, M., Nucci, C., Fumagalli, P., Jovine, L., Ottolenghi, S., and Taramelli, R. (2000) The gene encoding DRAP (BACE2), a glycosylated transmembrane protein of the aspartic protease family, maps to the down critical region. FEBS Lett. 468, 59-64
17. Bennett, B. D., Babu-Khan, S., Loeloff, R., Louis, J. C., Curran, E., Citron, M., and Vassar, R. (2000) Expression analysis of BACE2 in brain and peripheral tissues. J. Biol. Chem. 275, 20647-20651
18. Lin, X., Koelsch, G., Wu, S., Downs, D., Dashti, A., and Tang, J. (2000) Human aspartic protease memapsin 2 cleaves the beta-secretase site of beta-amyloid precursor protein. Proc. Natl. Acad. Sci. USA 97, 1456-1460
19. Solans, A., Estivill, X., and de La Luna, S. (2000) A new aspartyl protease on 21q22.3, BACE2, is highly similar to Alzheimer's amyloid precursor protein beta-secretase. Cytogenet. Cell Genet. 89, 177-184
20. Zhang, Z., Nadeau, P., Song, W., Donoviel, D., Yuan, M., Bernstein, A., and Yankner, B. A. (2000) Presenilins are required for gamma-secretase cleavage of beta-APP and transmembrane cleavage of Notch-1. Nat. Cell Biol. 2, 463-465
21. De Strooper, B., Annaert, W., Cupers, P., Saftig, P., Craessaerts, K., Mumm, J. S., Schroeter, E. H., Schrijvers, V., Wolfe, M. S., Ray, W. J., Goate, A., and Kopan, R. (1999) A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature 398, 518-522
22. Benjannet, S., Elagoz, A., Wickham, L., Mamarbachi, M., Munzer, J. S., Basak, A., Lazure, C., Cromlish, J. A., Sisodia, S., Checler, F., Chretien, M., and Seidah, N. G. (2001) Post-translational processing of beta-secretase (beta-amyloid-converting enzyme) and its ectodomain shedding. the pro-and transmembrane/cytosolic domains affect its cellular activity and amyloid-beta production. J. Biol. Chem. 276, 10879-10887
23. Bennett, B. D., Denis, P., Haniu, M., Teplow, D. B., Kahn, S., Louis, J.-C., Citron, M., and Vassar, R. (2000) A Furin-like convertase mediates propeptide cleavage of BACE, the Alzheimer's beta-secretase. J. Biol. Chem. 275, 37712-37717
24. Capell, A., Steiner, H., Willem, M., Kaiser, H., Meyer, C., Walter, J., Lammich, S., Multhaup, G., and Haass, C. (2000) Maturation and pro-peptide cleavage of beta-secretase. J. Biol. Chem. 275, 30849-30854
25. Creemers, J. W. M., Ines Dominguez, D., Plets, E., Serneels, L., Taylor, N. A., Multhaup, G., Craessaerts, K., Annaert, W., and De Strooper, B. (2001) Processing of beta-secretase by Furin and other members of the proprotein convertase family. J. Biol. Chem. 276, 4211-4217
26. Shi, X. P., Chen, E., Yin, K. C., Na, S., Garsky, V. M., Lai, M. T., Li, Y. M., Platchek, M., Register, R. B., Sardana, M. K., et al. (2001) The pro domain of beta-secretase does not confer strict zymogen-like properties but does assist proper folding of the protease domain. J. Biol. Chem. 276, 10366-10373
27. Huse, J. T., Pijak, D. S., Leslie, G. J., Lee, V. M.-Y., and Doms, R. W. (2000) Maturation and endosomal targeting of beta-site amyloid precursor protein-cleaving enzyme. the Alzheimer's disease beta-secretase. J. Biol. Chem. 275, 33729-33737
28. Walter, J., Fluhrer, R., Hartung, B., Willem, M., Kaether, C., Capell, A., Lammich, S., Multhaup, G., and Haass, C. (2001) Phosphorylation regulates intracellular trafficking of beta-secretase. J. Biol. Chem. 276, 14634-14641
29. Charlwood, J., Dingwall, C., Matico, R., Hussain, I., Johanson, K., Moore, S., Powell, D. J., Skehel, J. M., Ratcliffe, S., Clarke, B., et al. (2001) Characterization of the glycosylation profiles of Alzheimer's beta-secretase protein Asp-2 expressed in a variety of cell lines. J. Biol. Chem. 276, 16739-16748
30. Haniu, M., Denis, P., Young, Y., Mendiaz, E. A., Fuller, J., Hui, J. O., Bennett, B. D., Kahn, S., Ross, S., Burgess, T., et al. (2000) Characterization of Alzheimer's beta-secretase protein BACE. A pepsin family member with unusual properties. J. Biol. Chem. 275, 21099-21106
31. Qing, H., Zhou, W., Christensen, M. A., Sun, X., Tong, Y., and Song, W. (2004) Degradation of BACE by the ubiquitin-proteasome pathway. FASEB J. 18, 1571-1573
32. Li, Y., Zhou, W., Tong, Y., He, G., and Song, W. (2006) Control of APP processing and Abeta generation level by BACE1 enzymatic activity and transcription. FASEB J. 20, 285-292
33. Zhou, W., and Song, W. (2006) Leaky scanning and reinitiation regulate BACE1 gene expression. Mol. Cell. Biol. 26, 3353-3364
34. Cai, X. D., Golde, T. E., and Younkin, S. G. (1993) Release of excess amyloid beta protein from a mutant amyloid beta protein precursor. Science 259, 514-516
35. 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 beta-amyloid precursor protein in familial Alzheimer's disease increases beta-protein production. Nature 360, 672-674
36. Cruts, M., Dermaut, B., Rademakers, R., Roks, G., Van den Broeck, M., Munteanu, G., van Duijn, C. M., and Van Broeckhoven, C. (2001) Amyloid beta secretase gene (BACE) is neither mutated in nor associated with early-onset Alzheimer's disease. Neurosci. Lett. 313, 105-107
37. Nicolaou, M., Song, Y. Q., Sato, C. A., Orlacchio, A., Kawarai, T., Medeiros, H., Liang, Y., Sorbi, S., Richard, E., Rogaev, E. I., et al. (2001) Mutations in the open reading frame of the beta-site APP cleaving enzyme (BACE) locus are not a common cause of Alzheimer's disease. Neurogenetics 3, 203-206
38. Russo, C., Schettini, G., Saido, T. C., Hulette, C., Lippa, C., Lannfelt, L., Ghetti, B., Gambetti, P., Tabaton, M., and Teller, J. K. (2000) Presenilin-1 mutations in Alzheimer's disease. Nature 405, 531-532
39. Fukumoto, H., Cheung, B. S., Hyman, B. T., and Irizarry, M. C. (2002) Beta-secretase protein and activity are increased in the neocortex in Alzheimer disease. Arch. Neurol. 59, 1381-1389
40. Fukumoto, H., Rosene, D. L., Moss, M. B., Raju, S., Hyman, B. T., and Irizarry, M. C. (2004) Beta-secretase activity increases with aging in human, monkey, and mouse brain. Am. J. Pathol. 164, 719-725
41. Holsinger, R. M., McLean, C. A., Beyreuther, K., Masters, C. L., and Evin, G. (2002) Increased expression of the amyloid precursor beta-secretase in Alzheimer's disease. Ann. Neurol. 51, 783-786
42. Yang, L. B., Lindholm, K., Yan, R., Citron, M., Xia, W., Yang, X. L., Beach, T., Sue, L., Wong, P., Price, D., Li, R., and Shen, Y. (2003) Elevated beta-secretase expression and enzymatic activity detected in sporadic Alzheimer disease. Nat. Med. 9, 3-4
43. Sun, X., Wang, Y., Qing, H., Christensen, M. A., Liu, Y., Zhou, W., Tong, Y., Xiao, C., Huang, Y., Zhang, S., et al. (2005) Distinct transcriptional regulation and function of the human BACE2 and BACE1 genes. FASEB J. 19, 739-749
44. Ostermann, N., Eder, J., Eidhoff, U., Zink, F., Hassiepen, U., Worpenberg, S., Maibaum, J., Simic, O., Hommel, U., and Gerhartz, B. (2006) Crystal structure of human BACE2 in complex with a hydroxyethylamine transition-state inhibitor. J. Mol. Biol. 355, 249-261
45. Hussain, I., Christie, G., Schneider, K., Moore, S., and Dingwall, C. (2001) Prodomain processing of Asp1 (BACE2) is autocatalytic. J. Biol. Chem. 276, 23322-23328
46. Farzan, M., Schnitzler, C. E., Vasilieva, N., Leung, D., and Choe, H. (2000) BACE2, a beta-secretase homolog, cleaves at the beta site and within the amyloid-beta region of the amyloid-beta precursor protein. Proc. Natl. Acad. Sci. USA 97, 9712-9717
47. Hussain, I., Powell, D. J., Howlett, D. R., Chapman, G. A., Gilmour, L., Murdock, P. R., Tew, D. G., Meek, T. D., Chapman, C., Schneider, K., et al. (2000) ASP1 (BACE2) cleaves the amyloid precursor protein at the beta-secretase site. Mol. Cell Neurosci. 16, 609-619
48. Basi, G., Frigon, N., Barbour, R., Doan, T., Gordon, G., McConlogue, L., Sinha, S., and Zeller, M. (2003) Antagonistic effects of beta-site amyloid precursor protein-cleaving enzymes 1 and 2 on beta-amyloid peptide production in cells. J. Biol. Chem. 278, 31512-31520
49. Yan, R., Munzner, J. B., Shuck, M. E., and Bienkowski, M. J. (2001) BACE2 functions as an alternative alpha-secretase in cells. J. Biol. Chem. 276, 34019-34027
50. Luo, Y., Bolon, B., Damore, M. A., Fitzpatrick, D., Liu, H., Zhang, J., Yan, Q., Vassar, R., and Citron, M. (2003) BACE1 (beta-secretase) knockout mice do not acquire compensatory gene expression changes or develop neural lesions over time. Neurobiol. Dis. 14, 81-88
51. Dominguez, D., Tournoy, J., Hartmann, D., Huth, T., Cryns, K., Deforce, S., Serneels, L., Camacho, I. E., Marjaux, E., Craessaerts, K., et al. (2005) Phenotypic and biochemical analyses of BACE1- and BACE2-deficient mice. J. Biol. Chem. 280, 30797-30806
52. Christensen, M. A., Zhou, W., Qing, H., Lehman, A., Philipsen, S., and Song, W. (2004) Transcriptional regulation of BACE1, the beta-amyloid precursor protein beta-secretase, by Sp1. Mol. Cell. Biol. 24, 865-874
53. Dittgen, T., Nimmerjahn, A., Komai, S., Licznerski, P., Waters, J., Margrie, T. W., Helmchen, F., Denk, W., Brecht, M., and Osten, P. (2004) Lentivirus-based genetic manipulations of cortical neurons and their optical and electrophysiological monitoring in vivo. Proc. Natl. Acad. Sci. USA 101, 18206-18211
54. Lois, C., Hong, E. J., Pease, S., Brown, E. J., and Baltimore, D. (2002) Germline transmission and tissue-specific expression of transgenes delivered by lentiviral vectors. Science 295, 868-872
55. Sturchler-Pierrat, C., Abramowski, D., Duke, M., Wiederhold, K. H., Mistl, C., Rothacher, S., Ledermann, B., Burki, K., Frey, P., Paganetti, P. A., et al. (1997) Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology. Proc. Natl. Acad. Sci. USA 94, 13287-13292
56. Van Dam, D., D'Hooge, R., Staufenbiel, M., Van Ginneken, C., Van Meir, F., and De Deyn, P. P. (2003) Age-dependent cognitive decline in the APP23 model precedes amyloid deposition. Eur. J. Neurosci. 17, 388-396
57. Podlisny, M. B., Lee, G., and Selkoe, D. J. (1987) Gene dosage of the amyloid beta precursor protein in Alzheimer's disease. Science 238, 669-671
58. Hong, L., Koelsch, G., Lin, X., Wu, S., Terzyan, S., Ghosh, A. K., Zhang, X. C., and Tang, J. (2000) Structure of the protease domain of memapsin 2 (beta-secretase) complexed with inhibitor. Science 290, 150-153
59. Hong, L., Turner, R. T., 3rd, Koelsch, G., Shin, D., Ghosh, A. K., and Tang, J. (2002) Crystal structure of memapsin 2 (beta-secretase) in complex with an inhibitor OM00-3. Biochemistry 41, 10963-10967
60. Goldin, L. R., and Gershon, E. S. (1993) Linkage of Alzheimer's disease to chromosome 21 and chromosome 19 markers: effect of age of onset assumptions. Genet. Epidemiol. 10, 449-454
61. Heston, L. L., Orr, H. T., Rich, S. S., and White, J. A. (1991) Linkage of an Alzheimer disease susceptibility locus to markers on human chromosome 21. Am J. Med. Genet 40, 449-453
62. Kehoe, P., Wavrant-De Vrieze, F., Crook, R., Wu, W. S., Holmans, P., Fenton, I., Spurlock, G., Norton, N., Williams, H., Williams, N., et al. (1999) A full genome scan for late onset Alzheimer's disease. Hum. Mol. Genet. 8, 237-245
63. Myers, A., Wavrant De-Vrieze, F., Holmans, P., Hamshere, M., Crook, R., Compton, D., Marshall, H., Meyer, D., Shears, S., Booth, J., et al. (2002) Full genome screen for Alzheimer disease: stage II analysis. Am. J. Med. Genet. 114, 235-244
64. Myllykangas, L., Wavrant-De Vrieze, F., Polvikoski, T., Notkola, I. L., Sulkava, R., Niinisto, L., Edland, S. D., Arepalli, S., Adighibe, O., Compton, D., et al. (2005) Chromosome 21 BACE2 haplotype associates with Alzheimer's disease: a twostage study. J. Neurol. Sci. 236, 17-24
65. Pericak-Vance, M. A., Bebout, J. L., Gaskell, P. C., Jr., Yamaoka, L. H., Hung, W. Y., Alberts, M. J., Walker, A. P., Bartlett, R. J., Haynes, C. A., Welsh, K. A., et al. (1991) Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage. Am. J. Hum. Genet. 48, 1034-1050
66. Blacker, D., Bertram, L., Saunders, A. J., Moscarillo, T. J., Albert, M. S., Wiener, H., Perry, R. T., Collins, J. S., Harrell, L. E., Go, R. C., et al. (2003) Results of a high-resolution genome screen of 437 Alzheimer's disease families. Hum. Mol. Genet. 12, 23-32