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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
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
Brain lipidomics: From functional landscape to clinical significance
Yoon, J. H., Seo, Y., Jo, Y. S., Lee, S., Cho, E., Cazenave-Gassiot, A., Shin, Y.-S., Moon, M. H., An, H. J., Wenk, M. R., et al. (2022) · Science Advances · doi:10.1126/sciadv.adc9317 · Cited by 324
Bosco, D., Fava, A., Plastino, M., Montalcini, T., & Pujia, A. (2011) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2011.01318.x · Cited by 283
Geekiyanage, H., & Chan, C. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.3883-11.2011 · Cited by 254
Jazvinšćak Jembrek, M., Hof, P. R., & Šimić, G. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/346783 · Cited by 244
Is Alzheimer’s disease a systemic disease?
Morris, J. K., Honea, R. A., Vidoni, E. D., Swerdlow, R. H., & Burns, J. M. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.04.012 · Cited by 219
Freude, S., Hettich, M. M., Schumann, C., Stöhr, O., Koch, L., Köhler, C., Udelhoven, M., Leeser, U., Müller, M., Kubota, N., et al. (2009) · The FASEB Journal · doi:10.1096/fj.09-132043 · Cited by 218
Han, X. (2005) · Current Alzheimer Research · doi:10.2174/1567205052772786 · Cited by 183
Lipid metabolism and storage in neuroglia: role in brain development and neurodegenerative diseases
Yang, D., Wang, X., Zhang, L., Fang, Y., Zheng, Q., Liu, X., Yu, W., Chen, S., Ying, J., & Hua, F. (2022) · Cell & Bioscience · doi:10.1186/s13578-022-00828-0 · Cited by 179
Mielke, M. M., Haughey, N. J., Bandaru, V. V. R., Schech, S., Carrick, R., Carlson, M. C., Mori, S., Miller, M. I., Ceritoglu, C., Brown, T., et al. (2010) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2010.03.014 · Cited by 170
Ko, M. H., & Puglielli, L. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m804901200 · Cited by 111
Self-citationTamboli, I. Y., Prager, K., Barth, E., Heneka, M., Sandhoff, K., & Walter, J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414525200 · Cited by 110
APP Function and Lipids: A Bidirectional Link
Grimm, M. O. W., Mett, J., Grimm, H. S., & Hartmann, T. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00063 · Cited by 104
Lipid metabolism in Alzheimer’s disease
Liu, Q., & Zhang, J. (2014) · Neuroscience Bulletin · doi:10.1007/s12264-013-1410-3 · Cited by 101
Costantini, C., Ko, M. H., Jonas, M. C., & Puglielli, L. (2007) · Biochemical Journal · doi:10.1042/bj20070040 · Cited by 99
Self-citationInflammasome-mediated innate immunity in Alzheimer’s disease
Venegas, C., & Heneka, M. T. (2019) · The FASEB Journal · doi:10.1096/fj.201900439 · Cited by 93
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
Cao, Y., Zhao, L.-W., Chen, Z.-X., & Li, S.-H. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1430465 · Cited by 65
Aging of the brain, neurotrophin signaling, and Alzheimer's disease: Is IGF1-R the common culprit?
Puglielli, L. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.01.010 · Cited by 61
Self-citationNeuronal human BACE1 knockin induces systemic diabetes in mice
Plucińska, K., Dekeryte, R., Koss, D., Shearer, K., Mody, N., Whitfield, P. D., Doherty, M. K., Mingarelli, M., Welch, A., Riedel, G., et al. (2016) · Diabetologia · doi:10.1007/s00125-016-3960-1 · Cited by 58
Reinhardt, S., Stoye, N., Luderer, M., Kiefer, F., Schmitt, U., Lieb, K., & Endres, K. (2018) · Scientific Reports · doi:10.1038/s41598-018-19577-7 · Cited by 58
Diverse roles of ceramide in the progression and pathogenesis of Alzheimer's disease
Chowdhury, M. R., Jin, H. K., & Bae, J.-S. (2022) · Biomedicines · doi:10.3390/biomedicines10081956 · Cited by 47
Morgan, A. R., Turic, D., Jehu, L., Hamilton, G., Hollingworth, P., Moskvina, V., Jones, L., Lovestone, S., Brayne, C., Rubinsztein, D. C., et al. (2007) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30509 · Cited by 42
The BACE1 product sAPPβ induces ER stress and inflammation and impairs insulin signaling
Botteri, G., Salvadó, L., Gumà, A., Lee Hamilton, D., Meakin, P. J., Montagut, G., Ashford, M. L. J., Ceperuelo-Mallafré, V., Fernández-Veledo, S., Vendrell, J., et al. (2018) · Metabolism · doi:10.1016/j.metabol.2018.03.005 · Cited by 39
MicroRNAs in brain cholesterol metabolism and their implications for Alzheimer's disease
Yoon, H., Flores, L. F., & Kim, J. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2016.04.020 · Cited by 23
Multiplatform Lipid Analysis of the Brain of Aging Mice by Mass Spectrometry
Panda, P., Ferreira, C. R., Cooper, B. R., Schaser, A. J., & Aryal, U. K. (2025) · Journal of Proteome Research · doi:10.1021/acs.jproteome.4c00688 · Cited by 19
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
