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Inhibition of glycosphingolipid biosynthesis reduces secretion of the beta-amyloid precursor protein and amyloid beta-peptide
Tamboli IY, Prager K, Barth E, Heneka M, Sandhoff K, Walter J.. The Journal of biological chemistry, 2005-05-27
Topic: Brain proteins, microglia and lab models
Alzheimer disease is associated with extracellular deposits of amyloid beta-peptides in the brain. Amyloid beta-peptides are generated by proteolytic processing of the beta-amyloid precursor protein by beta- and gamma-secretases. The cleavage by secretases occurs predominantly in post-Golgi secretory and endocytic compartments and is influenced by cholesterol, indicating a role of the membrane lipid composition in proteolytic processing of the beta-amyloid precursor protein.
Key findings
- Amyloid beta-peptides are generated by proteolytic processing of the beta-amyloid precursor protein by beta- and gamma-secretases.
- The cleavage by secretases occurs predominantly in post-Golgi secretory and endocytic compartments and is influenced by cholesterol, indicating a role of the membrane lipid composition in proteolytic processing of the beta-amyloid precursor protein.
- To analyze the role of glycosphingolipids in these processes we inhibited glycosyl ceramide synthase, which catalyzes the first step in glycosphingolipid biosynthesis.
- The depletion of glycosphingolipids markedly reduced the secretion of endogenous beta-amyloid precursor protein in different cell types, including human neuroblastoma SH-SY5Y cells.
Why it matters
In laboratory cells, blocking glycosphingolipid biosynthesis by inhibiting glycosyl ceramide synthase reduced secretion of amyloid precursor protein and amyloid β peptide. This is cell-based research and does not show a treatment, cure, or prevention for Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of biological chemistry) |
| Journal's citation record | 4 / 4 | Journal of Biological Chemistry: journal h-index 780 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2005 — older than 20 years, still counted |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 122 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.3 citations a year over 23 year(s) since 2005 |
| Impact for its field and year | 3 / 6 | Cited 5.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 1 / 4 | Cited 4 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Jochen Walter: h-index 67 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Bonn: institution h-index 1,072 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 15923191) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 41 / 100 | — |
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Read the original
- DOI: 10.1074/jbc.m414525200
- PubMed: 15923191
- Original source →
- Free full text: Journal of Biological Chemistry →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Tamboli, I. Y., Prager, K., Barth, E., Heneka, M., Sandhoff, K., & Walter, J. (2005). Inhibition of glycosphingolipid biosynthesis reduces secretion of the beta-amyloid precursor protein and amyloid beta-peptide. The Journal of biological chemistry. https://doi.org/10.1074/jbc.m414525200
Vancouver
Tamboli IY, Prager K, Barth E, Heneka M, Sandhoff K, Walter J. Inhibition of glycosphingolipid biosynthesis reduces secretion of the beta-amyloid precursor protein and amyloid beta-peptide. The Journal of biological chemistry. 2005. doi:10.1074/jbc.m414525200. PMID: 15923191.
BibTeX
@article{tamboli2005-15923191,
author = {Tamboli, I. Y. and Prager, K. and Barth, E. and Heneka, M. and Sandhoff, K. and Walter, J.},
title = {{Inhibition of glycosphingolipid biosynthesis reduces secretion of the beta-amyloid precursor protein and amyloid beta-peptide}},
journal = {The Journal of biological chemistry},
year = {2005},
doi = {10.1074/jbc.m414525200},
pmid = {15923191},
url = {https://doi.org/10.1074/jbc.m414525200}
}
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