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beta-Amyloid peptide and a 3-kDa fragment are derived by distinct cellular mechanisms.
Open accessAbstract
We have analyzed the cellular processing pathways which produce the 4-kDa amyloid beta-peptide (A beta) and a 3-kDa derivative (p3) of the beta-amyloid precursor protein (beta APP) found in conditioned media of tissue culture cells and in cerebrospinal fluid. Pulse-chase experiments reveal that both peptides are secreted in parallel with soluble beta APP (APPs); no precursor-product relation between A beta and p3 was found. The protease inhibitor leupeptin did not influence the production of either peptide. In contrast, the weak base ammonium chloride (NH4Cl) showed a dose-dependent inhibition of A beta production with less decrease in p3. A similar effect was observed using the monovalent ionophore monensin. Brefeldin A completely inhibited the generation of both peptides, indicating that proteases located in the endoplasmic reticulum or early Golgi are not sufficient for the production of the small peptides. Deletion of the beta APP cytoplasmic domain, which removes a consensus sequence that probably mediates reinternalization, caused an increase in secretion of both APPs and p3 and did not abolish A beta production. These observations suggest that completely mature beta APP within the late Golgi and/or at the cell surface is a prerequisite for A beta production but processing within the lysosome might not be directly required. p3 appears to derive from the 10-kDa C-terminal stub of beta APP following secretion of APPs.
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Cites
Amyloid β-peptide is produced by cultured cells during normal metabolism
Haass, C., Schlossmacher, M. G., Hung, A. Y., Vigo-Pelfrey, C., Mellon, A., Ostaszewski, B. L., Lieberburg, I., Koo, E. H., Schenk, D., Teplow, D. B., et al. (1992) · Nature · doi:10.1038/359322a0 · Cited by 1,921
Self-citationIsolation and quantification of soluble Alzheimer's β-peptide from biological fluids
Seubert, P., Vigo-Pelfrey, C., Esch, F., Lee, M., Dovey, H., Davis, D., Sinha, S., Schiossmacher, M., Whaley, J., Swindlehurst, C., et al. (1992) · Nature · doi:10.1038/359325a0 · Cited by 1,731
Self-citationProduction of the Alzheimer Amyloid β Protein by Normal Proteolytic Processing
Shoji, M., Golde, T. E., Ghiso, J., Cheung, T. T., Estus, S., Shaffer, L. M., Cai, X.-D., McKay, D. M., Tintner, R., Frangione, B., et al. (1992) · Science · doi:10.1126/science.1439760 · Cited by 1,447
Cited by
Alzheimer's Disease: Genes, Proteins, and Therapy
Selkoe, D. J. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.741 · Cited by 6,063
Self-citationVassar, 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) · Science · doi:10.1126/science.286.5440.735 · Cited by 3,876
Self-citationIntracellular amyloid-β in Alzheimer's disease
LaFerla, F. M., Green, K. N., & Oddo, S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2168 · Cited by 1,942
Trafficking and Proteolytic Processing of APP
Haass, C., Kaether, C., Thinakaran, G., & Sisodia, S. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006270 · Cited by 1,075
Self-citationAPP processing in Alzheimer’s disease.
Zhang, Y.-W., Thompson, R., Zhang, H., & Xu, H. (2011) · Molecular Brain · doi:10.1186/1756-6606-4-3 · Cited by 983
Lammich, S., Kojro, E., Postina, R., Gilbert, S., Pfeiffer, R., Jasionowski, M., Haass, C., & Fahrenholz, F. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.7.3922 · Cited by 975
Self-citationArrest of -Amyloid Fibril Formation by a Pentapeptide Ligand
Tjernberg, L. O., Näslund, J., Lindqvist, F., Johansson, J., Karlström, A. R., Thyberg, J., Terenius, L., & Nordstedt, C. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.15.8545 · Cited by 963
Cell biology of protein misfolding: the examples of Alzheimer's and Parkinson's diseases
Selkoe, D. J. (2004) · Nature Cell Biology · doi:10.1038/ncb1104-1054 · Cited by 863
Self-citationEvidence that production and release of amyloid beta-protein involves the endocytic pathway
Koo, E. H., & Squazzo, S. L. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)32449-3 · Cited by 829
Cellular processing of β-amyloid precursor protein and the genesis of amyloid β-peptide
Haass, C., & Selkoe, D. J. (1993) · Cell · doi:10.1016/0092-8674(93)90312-e · Cited by 686
Self-citationAndersen, O. M., Reiche, J., Schmidt, V., Gotthardt, M., Spoelgen, R., Behlke, J., von Arnim, C. A. F., Breiderhoff, T., Jansen, P., Wu, X., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503689102 · Cited by 655
Haass, C., Lemere, C. A., Capell, A., Citron, M., Seubert, P., Schenk, D., Lannfelt, L., & Selkoe, D. J. (1995) · Nature Medicine · doi:10.1038/nm1295-1291 · Cited by 592
Self-citationThe Alzheimer's disease Beta-secretase enzyme, BACE1
Cole, S. L., & Vassar, R. (2007) · Molecular Neurodegeneration · doi:10.1186/1750-1326-2-22 · Cited by 550
Borg, J.-P., Ooi, J., Levy, E., & Margolis, B. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.11.6229 · Cited by 477
η-Secretase processing of APP inhibits neuronal activity in the hippocampus
Willem, M., Tahirovic, S., Busche, M. A., Ovsepian, S. V., Chafai, M., Kootar, S., Hornburg, D., Evans, L. D. B., Moore, S., Daria, A., et al. (2015) · Nature · doi:10.1038/nature14864 · Cited by 398
Self-citationCataldo, A. M., Barnett, J. L., Berman, S. A., Li, J., Quarless, S., Bursztajn, S., Lippa, C., & Nixon, R. A. (1995) · Neuron · doi:10.1016/0896-6273(95)90324-0 · Cited by 379
Gabuzda, D., Busciglio, J., Chen, L. B., Matsudaira, P., & Yankner, B. A. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)36875-8 · Cited by 373
Citron, M., Vigo-Pelfrey, C., Teplow, D. B., Miller, C., Schenk, D., Johnston, J., Winblad, B., Venizelos, N., Lannfelt, L., & Selkoe, D. J. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.25.11993 · Cited by 366
Self-citationPortelius, E., Bogdanovic, N., Gustavsson, M. K., Volkmann, I., Brinkmalm, G., Zetterberg, H., Winblad, B., & Blennow, K. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0690-1 · Cited by 348
Lichtenthaler, S. F., Lemberg, M. K., & Fluhrer, R. (2018) · The EMBO Journal · doi:10.15252/embj.201899456 · Cited by 323
Amyloid‐Beta Interaction with Mitochondria
Pagani, L., & Eckert, A. (2011) · International Journal of Alzheimer’s Disease · doi:10.4061/2011/925050 · Cited by 309
Intracellular Generation and Accumulation of Amyloid β-Peptide Terminating at Amino Acid 42
Wild-Bode, C., Yamazaki, T., Capell, A., Leimer, U., Steiner, H., Ihara, Y., & Haass, C. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.26.16085 · Cited by 303
Self-citationAmino-terminal Deletions Enhance Aggregation of β-Amyloid Peptides in Vitro
Pike, C. J., Overman, M. J., & Cotman, C. W. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.41.23895 · Cited by 302
Gowing, E., Roher, A. E., Woods, A. S., Cotter, R. J., Chaney, M., Little, S. P., & Ball, M. J. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)78080-6 · Cited by 223
Liu, C.-C., Tsai, C.-W., Deak, F., Rogers, J., Penuliar, M., Sung, Y. M., Maher, J. N., Fu, Y., Li, X., Xu, H., et al. (2014) · Neuron · doi:10.1016/j.neuron.2014.08.048 · Cited by 222
Neurotherapeutic applications of nanoparticles in Alzheimer’s disease
Sahni, J. K., Doggui, S., Ali, J., Baboota, S., Dao, L., & Ramassamy, C. (2011) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.11.033 · Cited by 219
Serotonin 5-HT2a and 5-HT2c Receptors Stimulate Amyloid Precursor Protein Ectodomain Secretion
Nitsch, R. M., Deng, M., Growdon, J. H., & Wurtman, R. J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.8.4188 · Cited by 219
Implications of the serine protease HtrA1 in amyloid precursor protein processing
Grau, S., Baldi, A., Bussani, R., Tian, X., Stefanescu, R., Przybylski, M., Richards, P., Jones, S. A., Shridhar, V., Clausen, T., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501823102 · Cited by 215
The Role of APP Processing and Trafficking Pathways in the Formation of Amyloid β‐Proteina
SELKOE, D. J., YAMAZAKI, T., CITRON, M., PODLISNY, M. B., KOO, E. H., TEPLOW, D. B., & HAASS, C. (1996) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1996.tb34401.x · Cited by 205
Self-citationBorg, J.-P., Yang, Y., De Taddéo-Borg, M., Margolis, B., & Turner, R. S. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.24.14761 · Cited by 201
Schmidt, V., Sporbert, A., Rohe, M., Reimer, T., Rehm, A., Andersen, O. M., & Willnow, T. E. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m705073200 · Cited by 181
Turner, R. S., Suzuki, N., Chyung, A. S. C., Younkin, S. G., & Lee, V. M.-Y. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.15.8966 · Cited by 161
Endo‐lysosomal and autophagic dysfunction: a driving factor in Alzheimer's disease?
Whyte, L. S., Lau, A. A., Hemsley, K. M., Hopwood, J. J., & Sargeant, T. J. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.13935 · Cited by 150
Zhang, Z., Lee, C., Mandiyan, V., Borg, J., Margolis, B., Schlessinger, J., & Kuriyan, J. (1997) · The EMBO Journal · doi:10.1093/emboj/16.20.6141 · Cited by 140
Dysregulation of protein trafficking in neurodegeneration
Wang, X., Huang, T., Bu, G., & Xu, H. (2014) · Molecular Neurodegeneration · doi:10.1186/1750-1326-9-31 · Cited by 125
Chyung, J. H., & Selkoe, D. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304989200 · Cited by 111
Self-citationA non‐amyloidogenic function of BACE‐2 in the secretory pathway
Fluhrer, R., Capell, A., Westmeyer, G., Willem, M., Hartung, B., Condron, M. M., Teplow, D. B., Haass, C., & Walter, J. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00908.x · Cited by 95
Self-citationCathepsin D is involved in the clearance of Alzheimer's β‐amyloid protein
Hamazaki, H. (1996) · FEBS Letters · doi:10.1016/0014-5793(96)01087-3 · Cited by 92
Felsenstein, K. M., Hunihan, L. W., & Roberts, S. B. (1994) · Nature Genetics · doi:10.1038/ng0394-251 · Cited by 90
Endogenous Presenilin-1 Targets to Endocytic Rather Than Biosynthetic Compartments
Lah, J. J., & Levey, A. I. (2000) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.2000.0861 · Cited by 84
The Basic Biology of BACE1: A Key Therapeutic Target for Alzheimers Disease
Vassar, R., & Cole, S. (2007) · Current Genomics · doi:10.2174/138920207783769512 · Cited by 84
Prabhu, Y., Burgos, P. V., Schindler, C., Farías, G. G., Magadán, J. G., & Bonifacino, J. S. (2012) · Molecular Biology of the Cell · doi:10.1091/mbc.e11-11-0944 · Cited by 68
Bodendorf, U., Fischer, F., Bodian, D., Multhaup, G., & Paganetti, P. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008861200 · Cited by 58
Tan, J. Z. A., & Gleeson, P. A. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.005222 · Cited by 56
Lopez Sanchez, M. I. G., Waugh, H. S., Tsatsanis, A., Wong, B. X., Crowston, J. G., Duce, J. A., & Trounce, I. A. (2017) · Scientific Reports · doi:10.1038/s41598-017-10233-0 · Cited by 45
β-Amyloid Aggregation in Human Brains With Cerebrovascular Lesions
Aho, L., Jolkkonen, J., & Alafuzoff, I. (2006) · Stroke · doi:10.1161/01.str.0000248777.44128.93 · Cited by 40
Dodart, J.-C., Bales, K. R., Johnstone, E. M., Little, S. P., & Paul, S. M. (2002) · Brain Research · doi:10.1016/s0006-8993(02)03437-6 · Cited by 30
SORLA/SORL1, a neuronal sorting receptor implicated in Alzheimer’s disease
Willnow, T. E., Carlo, A.-S., Rohe, M., & Schmidt, V. (2010) · Reviews in the Neurosciences · doi:10.1515/revneuro.2010.21.4.315 · Cited by 20
Connop, B. P., Thies, R. L., Beyreuther, K., Ida, N., & Reiner, P. B. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.721457.x · Cited by 19
Hitschler, L., & Lang, T. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.101911 · Cited by 11
Metadata
- Authors
- Haass, C., Hung, A. Y., Schlossmacher, M. G., Teplow, D. B., & Selkoe, D. J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1993-02
- Volume
- 268
- Issue
- 5
- Pages
- 3021-3024
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1554535382
- Cited by
- 465
- References
- 3
- FWCI
- 22.88
- Type
- journal article
- Language
- en
- Open access
- hybrid
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