The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Ceramide Stabilizes β-Site Amyloid Precursor Protein-cleaving Enzyme 1 and Promotes Amyloid β-Peptide Biogenesis
Open accessAbstract
The lipid second messenger ceramide regulates several biochemical events that occur during aging. In addition, its level is highly elevated in the amyloid-burdened brains of Alzheimer's disease patients. Here, we analyzed the impact of aberrant ceramide levels on amyloid beta-peptide (Abeta) generation by using a cell-permeable analog of ceramide, C6-ceramide, and several biochemical inhibitors of the sphingomyelin/glycosphingolipid biosynthetic pathway. We found that C6-ceramide increased the biogenesis of Abeta by affecting beta-but not gamma-cleavage of the amyloid precursor protein. Similarly to C6-ceramide, increased levels of endogenous ceramide induced by neutral sphingomyelinase treatment also promoted the biogenesis of Abeta. Conversely, fumonisin B1, which inhibits the biosynthesis of endogenous ceramide, reduced Abeta production. Exogenous C6-ceramide restored both intracellular ceramide levels and Abeta generation in fumonisin B1-treated cells. These events were specific for amyloid precursor protein and were not associated with apoptotic cell death. Pulse-chase and time-course degradation experiments showed that ceramide post-translationally stabilizes the beta-secretase BACE1. Taken together, these data indicate that the lipid second messenger ceramide, which is elevated in the brains of Alzheimer's disease patients, increases the half-life of BACE1 and thereby promotes Abeta biogenesis.
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Cites
CNS synaptogenesis promoted by glia-derived cholesterol
Mauch, D. H., Nägler, K., Schumacher, S., Göritz, C., Müller, E.-C., Otto, A., & Pfrieger, F. W. (2001) · Science · doi:10.1126/science.294.5545.1354 · Cited by 1,711
Han, X., M. Holtzman, D., W. McKeel, D., Kelley, J., & Morris, J. C. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00997.x · Cited by 626
Oxidative stress increases expression and activity of BACE in NT2 neurons
Tamagno, E., Bardini, P., Obbili, A., Vitali, A., Borghi, R., Zaccheo, D., Pronzato, M. A., Danni, O., Smith, M. A., Perry, G., et al. (2002) · Neurobiology of Disease · doi:10.1006/nbdi.2002.0515 · Cited by 385
Is Alzheimer’s disease inevitable with age?
Morris, J. C. (1999) · Journal of Clinical Investigation · doi:10.1172/jci8560 · Cited by 56
Cited by
Linking lipids to Alzheimer's disease: cholesterol and beyond
Di Paolo, G., & Kim, T.-W. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3012 · Cited by 972
The 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
Deregulation of sphingolipid metabolism in Alzheimer’s disease
He, X., Huang, Y., Li, B., Gong, C.-X., & Schuchman, E. H. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.05.010 · Cited by 516
Dinkins, M. B., Dasgupta, S., Wang, G., Zhu, G., & Bieberich, E. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.02.012 · Cited by 494
Yin, F. (2023) · The FEBS Journal · doi:10.1111/febs.16344 · Cited by 441
Metadata
- Authors
- Puglielli, L., Ellis, B. C., Saunders, A. J., & Kovacs, D. M.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-05
- Volume
- 278
- Issue
- 22
- Pages
- 19777-19783
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2112336037
- Cited by
- 265
- References
- 4
- FWCI
- 4.70
- Type
- journal article
- Language
- en
- Status
- Retracted
- Open access
- hybrid
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- CoChat. (2026). Citation check: Ceramide Stabilizes β-Site Amyloid Precursor Protein-cleaving Enzyme 1 and Promotes Amyloid β-Peptide Biogenesis. https://app.cochat.ai/papers/10.1074/jbc.m300466200
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- Puglielli, L., Ellis, B. C., Saunders, A. J., & Kovacs, D. M. (2003). Ceramide Stabilizes β-Site Amyloid Precursor Protein-cleaving Enzyme 1 and Promotes Amyloid β-Peptide Biogenesis. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m300466200
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