DOI: 10.1093/embo-reports/kvf124. A γ‐secretase inhibitor blocks Notch signaling <i>in vivo</i> and causes a severe neurogenic phenotype in zebrafish

A γ‐secretase inhibitor blocks Notch signaling in vivo and causes a severe neurogenic phenotype in zebrafish

10.1093/embo-reports/kvf124

Crossref journal-article

Springer Science and Business Media LLC

EMBO reports (297)

Abstract

Inhibition of amyloid β‐peptide (Aβ) production by blocking γ‐secretase activity is at present one of the most promising therapeutic strategies to slow progression of Alzheimer's disease pathology. γ‐secretase inhibitors apparently block Aβ generation via interference with presenilin (PS) function. Besides being an essential component of the γ‐secretase complex, PS itself may be an aspartyl protease with γ‐secretase activity, which is not only required for Aβ production but also for a similar proteolytic process involved in Notch signaling. Here we demonstrate that treatment of zebrafish embryos with a known γ‐secretase inhibitor affects embryonic development in a manner indistinguishable from Notch signaling deficiencies at morphological, molecular and biochemical levels. This indicates severe side‐effects of γ‐secretase inhibitors in any Notch‐dependent cell fate decision and demonstrates that the zebrafish is an ideal vertebrate system to validate compounds that selectively affect Aβ production, but not Notch signaling, under in vivo conditions.

Bibliography

Geling, A., Steiner, H., Willem, M., BallyâCuif, L., & Haass, C. (2002). A Î³âsecretase inhibitor blocks Notch signaling in vivo and causes a severe neurogenic phenotype in zebrafish. EMBO Reports, 3(7), 688â694. Portico.

Authors 5

Andrea Geling (first)
Harald Steiner (additional)
Michael Willem (additional)
Laure Bally‐Cuif (additional)
Christian Haass (additional)

References 56 Referenced 437

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Dates

Type	When
Created	23 years ago (July 28, 2002, 6:39 p.m.)
Deposited	1 year, 8 months ago (Dec. 18, 2023, 3:55 p.m.)
Indexed	1 month ago (July 25, 2025, 6:53 a.m.)
Issued	23 years, 1 month ago (July 1, 2002)
Published	23 years, 1 month ago (July 1, 2002)
Published Online	23 years, 1 month ago (July 1, 2002)
Published Print	23 years, 1 month ago (July 1, 2002)

Funders 0

None

BibTeX

@article{Geling_2002, title={A γ‐secretase inhibitor blocks Notch signaling in vivo and causes a severe neurogenic phenotype in zebrafish}, volume={3}, ISSN={1469-3178}, url={http://dx.doi.org/10.1093/embo-reports/kvf124}, DOI={10.1093/embo-reports/kvf124}, number={7}, journal={EMBO reports}, publisher={Springer Science and Business Media LLC}, author={Geling, Andrea and Steiner, Harald and Willem, Michael and Bally‐Cuif, Laure and Haass, Christian}, year={2002}, month=jul, pages={688–694} }

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