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A γ‐secretase inhibitor blocks Notch signaling in vivo and causes a severe neurogenic phenotype in zebrafish
Open accessAbstract
Inhibition of amyloid beta-peptide (Abeta) production by blocking gamma-secretase activity is at present one of the most promising therapeutic strategies to slow progression of Alzheimer's disease pathology. gamma-secretase inhibitors apparently block Abeta generation via interference with presenilin (PS) function. Besides being an essential component of the gamma-secretase complex, PS itself may be an aspartyl protease with gamma-secretase activity, which is not only required for Abeta production but also for a similar proteolytic process involved in Notch signaling. Here we demonstrate that treatment of zebrafish embryos with a known gamma-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 gamma-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 Abeta production, but not Notch signaling, under in vivo conditions.
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“DAPT, which prevents Notch cleavage and subsequent signaling by its intracellular domain, NICD”
From HB-EGF is Necessary and Sufficient for Müller Glia Dedifferentiation and Retina Regeneration (2012) · cites this paper as Geling et al., 2002
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Stages of embryonic development of the zebrafish
Kimmel, C. B., Ballard, W. W., Kimmel, S. R., Ullmann, B., & Schilling, T. F. (1995) · Developmental Dynamics · doi:10.1002/aja.1002030302 · Cited by 12,037
A presenilin-1-dependent γ-secretase-like protease mediates release of Notch intracellular domain
De Strooper, B., Annaert, W., Cupers, P., Saftig, P., Craessaerts, K., Mumm, J. S., Schroeter, E. H., Schrijvers, V., Wolfe, M. S., Ray, W. J., et al. (1999) · Nature · doi:10.1038/19083 · Cited by 2,100
Wolfe, M. S., Xia, W., Ostaszewski, B. L., Diehl, T. S., Kimberly, W. T., & Selkoe, D. J. (1999) · Nature · doi:10.1038/19077 · Cited by 1,959
Citron, M., Oltersdorf, T., Haass, C., McConlogue, L., Hung, A. Y., Seubert, P., Vigo-Pelfrey, C., Lieberburg, I., & Selkoe, D. J. (1992) · Nature · doi:10.1038/360672a0 · Cited by 1,757
Self-citationNotch-1 signalling requires ligand-induced proteolytic release of intracellular domain
Schroeter, E. H., Kisslinger, J. A., & Kopan, R. (1998) · Nature · doi:10.1038/30756 · Cited by 1,624
The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Aβ protofibril formation
Nilsberth, C., Westlind-Danielsson, A., Eckman, C. B., Condron, M. M., Axelman, K., Forsell, C., Stenh, C., Luthman, J., Teplow, D. B., Younkin, S. G., et al. (2001) · Nature Neuroscience · doi:10.1038/nn0901-887 · Cited by 1,209
Amyloid β-Protein Fibrillogenesis
Walsh, D. M., Lomakin, A., Benedek, G. B., Condron, M. M., & Teplow, D. B. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.35.22364 · Cited by 1,156
Notch Signaling: From the Outside In
Mumm, J. S., & Kopan, R. (2000) · Developmental Biology · doi:10.1006/dbio.2000.9960 · Cited by 964
Thisse, C., Thisse, B., Schilling, T. F., & Postlethwait, J. H. (1993) · Development · doi:10.1242/dev.119.4.1203 · Cited by 877
Functional gamma‐secretase inhibitors reduce beta‐amyloid peptide levels in brain
Dovey, H. F., John, V., Anderson, J. P., Chen, L. Z., Andrieu, P. D. S. I., Fang, L. Y., Freedman, S. B., Folmer, B., Goldbach, E. G., Holsztynska, E. J., et al. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00012.x · Cited by 870
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Items 301–400 of 498
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Kugler, E., Frost, J., Silva, V., Plant, K., Chhabria, K., Chico, T. J. A., & Armitage, P. A. (2022) · Development · doi:10.1242/dev.199720 · Cited by 22
Distinct pathways drive anterior hypoblast specification in the implanting human embryo
Weatherbee, B. A. T., Weberling, A., Gantner, C. W., Iwamoto-Stohl, L. K., Barnikel, Z., Barrie, A., Campbell, A., Cunningham, P., Drezet, C., Efstathiou, P., et al. (2024) · Nature Cell Biology · doi:10.1038/s41556-024-01367-1 · Cited by 24
Ohguro, Y., Takata, H., & Kominami, T. (2011) · Development Growth & Differentiation · doi:10.1111/j.1440-169x.2010.01233.x · Cited by 24
“DAPT is a reagent that prevents presenilin proteins from cleaving Notch to produce intracellular domain (Mumm & Kopan 2000; Geling et al. 2002), which enters the nucleus to activate downstream genes.”
BackgroundUngerer, P., Eriksson, B., & Stollewerk, A. (2012) · Developmental Biology · doi:10.1016/j.ydbio.2012.08.025 · Cited by 24
“We inhibited Notch activation using the g-secretase inhibitor DAPT (Geling et al., 2002; Pueyo et al., 2008).”
MethodSmall GTPase RhoE/Rnd3 Is a Critical Regulator of Notch1 Signaling
Zhu, Z., Todorova, K. A., Lee, K. K., Wang, J., Kwon, E., Kehayov, I. R., Kim, H.-G., Kolev, V. N., Dotto, G. P., Lee, S. W., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-12-0452 · Cited by 24
Iulianella, A., Sharma, M., Heuvel, G. B. V., & Trainor, P. A. (2009) · Development · doi:10.1242/dev.032128 · Cited by 24
“We cultured mouse embryos at E11 for 16 hours in the presence of either DMSO (carrier control) or 10 μM DAPT, which prevents γsecretase-mediated cleavage of Notch and blocks Notch signaling (Geling et al., 2002).”
MethodConstitutive JAK2/STAT1 activation regulates endogenous BACE1 expression in neurons.
Cho, H., Jin, S., Son, S., Kim, Y. W., Hwang, J.-Y., Hong, H., & Mook-Jung, I. (2009) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1016/j.bbrc.2009.06.006 · Cited by 29
Uribe, R. A., Kwon, T., Marcotte, E. M., & Gross, J. M. (2012) · Developmental Biology · doi:10.1016/j.ydbio.2012.08.032 · Cited by 24
“Embryos treated with DAPT exhibited phenotypes characteristic of Notch inhibition, i.e., disrupted somite morphology (Geling et al., 2002; Amsterdam et al., 2004; van Eeden et al., 1996; data not shown), and, in the retina, an expansion of RGCs (Supp.”
BackgroundMethodInfluentialTamagawa, Y., Ishimura, N., Uno, G., Aimi, M., Oshima, N., Yuki, T., Sato, S., Ishihara, S., & Kinoshita, Y. (2015) · Laboratory Investigation · doi:10.1038/labinvest.2015.137 · Cited by 23
Matsuda, M., Rand, K., Palardy, G., Shimizu, N., Ikeda, H., Nogare, D. D., Itoh, M., & Chitnis, A. B. (2016) · Development · doi:10.1242/dev.138743 · Cited by 23
“We treated embryo with DAPT, a γ-secretase inhibitor (Geling et al., 2002), to block Notch signaling.”
MethodKanungo, J., Zheng, Y., Amin, N. D., & Pant, H. C. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05551.x · Cited by 23
“2001) and, as a consequence, efficiently prevents activation of the Notch response (Sastre et al. 2001; Geling et al. 2002) and enhances neuronal differentiation of embryonic stem cell-derived embryoid bodies (Crawford and Roelink 2007).”
InfluentialOsathanon, T., Manokawinchoke, J., Egusa, H., & Pavasant, P. (2017) · Journal of Oral Science · doi:10.2334/josnusd.16-0552 · Cited by 22
Progenitor cell maturation in the developing vertebrate retina
Yang, H., Silva, A. O., Koyano‐Nakagawa, N., & McLoon, S. C. (2009) · Developmental Dynamics · doi:10.1002/dvdy.22116 · Cited by 22
“In other embryos, one eye was injected with a c-secretase inhibitor, DAPT (N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester; from Sigma-Aldrich), to disrupt Notch signaling as described previously (Geling et al., 2002; Nelson et al., 2006).”
Methodda Silva, M. A. S., Tee, J.-M., Paridaen, J. T. M. L., Brouwers, A., Runtuwene, V., Živković, D., Diks, S. H., Guardavaccaro, D., & Peppelenbosch, M. P. (2010) · PLoS ONE · doi:10.1371/journal.pone.0014023 · Cited by 21
Functional analysis of Hairy genes in Xenopus neural crest initial specification and cell migration
Vega‐López, G. A., Bonano, M., Tríbulo, C., Fernández, J. P., Aguero, T. H., & Aybar, M. J. (2015) · Developmental Dynamics · doi:10.1002/dvdy.24295 · Cited by 20
“To assess Notch activity, explants of neural crest embryos were cultured with 100 mM of DAPT (N-[N-(3,5-DifluorophenacetylL-alanyl)]-S-phenylglycine t-Butyl Ester, Sigma, St Louis, MO).”
MethodInfluentialDiosgenin: Mechanistic Insights on its Anti-inflammatory Effects
Karami‐Mohajeri, S., Mohammadinejad, R., Ashrafizadeh, M., Mohamadi, N., Mohajeri, M., & Sharififar, F. (2021) · Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry · doi:10.2174/1871523021666220328121721 · Cited by 20
Tando, Y., Fujiwara, K., Yashiro, T., & Kikuchi, M. (2012) · Cell and Tissue Research · doi:10.1007/s00441-012-1532-3 · Cited by 20
“The intracellular activation of Notch signaling requires the binding of the transmembrane protein Notch receptor and its ligand in neighboring cells, followed by the proteolytic release of the Notch intracellular domain (NICD) to assemble a transcription complex that activates downstream target genes (De Strooper et a…”
Banote, R. K., Edling, M., Eliassen, F., Kettunen, P., Zetterberg, H., & Abramsson, A. (2016) · Developmental Biology · doi:10.1016/j.ydbio.2016.03.012 · Cited by 20
“Notch signaling was chemically inhibited by DAPT (N-[N-(3,5-Difluorophenacetyl-l-alanyl]S-phenylglycine-t-butyl ester), a γ-secretase blocker (Geling et al., 2002; Song et al., 2010).”
MethodSmall Molecules That Inhibit Notch Signaling
de Kloe, G. E., & Strooper, B. D. (2014) · Methods in molecular biology · doi:10.1007/978-1-4939-1139-4_23 · Cited by 20
Carra, S., Sangiorgio, L., Pelucchi, P., Cermenati, S., Mezzelani, A., Martino, V., Palizban, M., Albertini, A., Götte, M., Kehler, J., et al. (2017) · Journal of Cellular Physiology · doi:10.1002/jcp.26032 · Cited by 20
Quéléver, G., Kachidian, P., Melon, C., Garino, C., Laras, Y., Pietrancosta, N., Sheha, M. M., & Kraus, J. L. (2005) · Organic & Biomolecular Chemistry · doi:10.1039/b504988a · Cited by 20
Reawakening Atlas: Chemical Approaches To Repair or Replace Dysfunctional Musculature
Jung, D., & Williams, D. R. (2012) · ACS Chemical Biology · doi:10.1021/cb3003368 · Cited by 19
Serra, C., Liu, H., Qian, J., Mori, M., Lü, J., & Cardoso, W. V. (2022) · iScience · doi:10.1016/j.isci.2022.104751 · Cited by 19
Mukhi, D., Kolligundla, L. P., Maruvada, S., Nishad, R., & Pasupulati, A. K. (2022) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2022.119391 · Cited by 19
Chatzeli, L., Bordeu, I., Han, S., Bisetto, S., Waheed, Z., Koo, B., Alcolea, M. P., & Simons, B. D. (2023) · Developmental Cell · doi:10.1016/j.devcel.2022.12.009 · Cited by 19
Assessing Neuroprotective Agents for Aβ-Induced Neurotoxicity
Forest, K. H., & Nichols, R. A. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2019.05.013 · Cited by 19
Transgenic analysis of the medaka mesp‐b enhancer in somitogenesis
Terasaki, H., Murakami, R., Yasuhiko, Y., Shin‐I, T., Kohara, Y., Saga, Y., & Takeda, H. (2006) · Development Growth & Differentiation · doi:10.1111/j.1440-169x.2006.00853.x · Cited by 19
“6J,L), as observed in zebrafish (Geling et al. 2002), whereas disulfiram treatment occasionally caused a disturbance in boundary formation and left–right asymmetric somitogenesis.”
InfluentialAnalogue and Conformational Studies on Peptides, Hormones and Other Biologically Active Peptides
Penke, B., Tóth, G. K., & Váradi, G. (2006) · Royal Society of Chemistry eBooks · doi:10.1039/9781847555250-00129 · Cited by 19
Evolution and Developmental Diversity of Skin Spines in Pufferfishes
Shono, T., Thiery, A. P., Cooper, R. L., Kurokawa, D., Britz, R., Okabe, M., & Fraser, G. J. (2019) · iScience · doi:10.1016/j.isci.2019.06.003 · Cited by 19
“Furthermore, treatment with the g-secretase complex and Notch pathway inhibitor, DAPT (Geling et al., 2002) (25 mM), resulted in abnormal spine morphogenesis and a 40% reduction in spine number in the ventral region of Takifugu (Figures 6C and 6L).”
MethodInfluentialZebrafish Numb and Numblike Are Involved in Primitive Erythrocyte Differentiation
Bresciani, E., Confalonieri, S., Cermenati, S., Cimbro, S., Foglia, E. A., Beltrame, M., Fiore, P. P. D., & Cotelli, F. (2010) · PLoS ONE · doi:10.1371/journal.pone.0014296 · Cited by 18
Thambyrajah, R., Ucanok, D., Jalali, M. S., Hough, Y., Wilkinson, R. N., McMahon, K., Moore, C., & Gering, M. (2016) · Developmental Biology · doi:10.1016/j.ydbio.2016.07.010 · Cited by 17
“To determine whether gfi1aa expression in the vDA required the Notch pathway, qmc551;gata1: dsRed embryos were either treated with the γ-secretase inhibitor DAPM (Geling et al., 2002) or injected with the Rbpja/b morpholino (Sieger et al.”
MethodNotch-mediated inhibition of neurogenesis is required for zebrafish spinal cord morphogenesis
Sharma, P., Saraswathy, V. M., Xiang, L., & Fürthauer, M. (2019) · Scientific Reports · doi:10.1038/s41598-019-46067-1 · Cited by 18
Tokuoka, M., Kumano, G., & Nishida, H. (2007) · Development Genes and Evolution · doi:10.1007/s00427-007-0160-5 · Cited by 18
“DAPT inhibits γ-secretase (Geling et al. 2002).”
Ryou, M., Mallet, R. T., Metzger, D. B., & Jung, M. E. (2017) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00050.2017 · Cited by 18
“Presenilin 1 is the catalytic subunit of -secretase (19), a protease that cleaves APP, yielding A 40 and A 42.”
BackgroundRaciti, M., Salma, J., Spulber, S. D., Gaudenzi, G., Khalajzeyqami, Z., Conti, M., Anderlid, B., Falk, A., Hermanson, O., & Ceccatelli, S. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00593 · Cited by 18
“DAPT efficiently blocks the presenilin–γ-secretase complex (Dovey et al., 2001) and, consequently, prevents the Notch response activation (Geling et al., 2002; Crawford and Roelink, 2007).”
BackgroundEffect of presenilins in the apoptosis of thymocytes and homeostasis of CD8+ T cells
Maraver, A., Tadokoro, C. E., Badura, M. L., Shen, J., Serrano, M., & Lafaille, J. J. (2007) · Blood · doi:10.1182/blood-2007-01-070359 · Cited by 18
Jagged1 protein processing in the developing mammalian lens
Azimi, M., & Brown, N. L. (2019) · Biology Open · doi:10.1242/bio.041095 · Cited by 17
“…in B3 cells by treating them with N-[N-(3,5-difluorophenacetyl)-Lalanyl]-S-phenylglycine t-butyl ester (DAPT), which binds to the C-terminus of Psen proteins and effectively blocks Notch receptor intracellular domain production (Dovey et al., 2001; Geling et al., 2002; Morohashi et al., 2006).”
BackgroundCerebrovascular endothelial cells form transient Notch‐dependent cystic structures in zebrafish
Kugler, E., van Lessen, M., Daetwyler, S., Chhabria, K., Savage, A. M., Silva, V., Plant, K., MacDonald, R. B., Huisken, J., Wilkinson, R. N., et al. (2019) · EMBO Reports · doi:10.15252/embr.201847047 · Cited by 16
“Notch signalling was inhibited using 50 lM DAPT (SigmaAldrich) for 12 h from 84 to 96 hpf [79].”
MethodcMyc-p53 feedback mechanism regulates the dynamics of T lymphocytes in the immune response
Madapura, H. S., Salamon, D., Wiman, K. G., Laı́n, S., Klein, E., & Nagy, N. (2016) · Cell Cycle · doi:10.1080/15384101.2016.1160975 · Cited by 18
“the indirect inhibition of Notch by DAPT, a g-secretase inhibitor.(37,24) Treatment with DAPT lowered cMyc levels and proliferation of activated T cells.”
BackgroundFoster, S., Teo, Y. V., Neretti, N., Oulhen, N., & Wessel, G. M. (2019) · Molecular Reproduction and Development · doi:10.1002/mrd.23181 · Cited by 17
CNS myelin protein 36K regulates oligodendrocyte differentiation through Notch
Nagarajan, B., Harder, A., Japp, A. S., Häberlein, F., Mingardo, E., Kleinert, H., Yilmaz, Ö., Zoons, A., Rau, B., Christ, A., et al. (2019) · Glia · doi:10.1002/glia.23732 · Cited by 19
Current Experimental Therapy for Alzheimers Disease
Chen, S., Zhang, X.-J., Li, L., & Le, W.-D. (2007) · Current Neuropharmacology · doi:10.2174/157015907780866901 · Cited by 17
“Side effect caused by disrupted Notch receptor signaling pathway has been reported in zebrafish model [33].”
BackgroundCheng, Y., Huang, Y.-C., Yeh, T., Shih, H., Lin, C., Lin, S., Chiu, C., Huang, C.-W., & Jiang, Y. (2015) · Neural Development · doi:10.1186/s13064-015-0055-5 · Cited by 17
“This result was further confirmed by the γ-secretase inhibitor, N-[N-(3,5difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), which has been shown to efficiently block Notch signaling at different time-points [21].”
ResultLaras, Y., Quéléver, G., Garino, C., Pietrancosta, N., Sheha, M. M., Bihel, F. J. ‐., Wolfe, M. S., & Kraus, J. (2005) · Organic & Biomolecular Chemistry · doi:10.1039/b415090b · Cited by 17
Notch-mediated re-specification of neuronal identity during central nervous system development
Engerer, P., Petridou, E., Williams, P. R., Suzuki, S. C., Yoshimatsu, T., Portugues, R., Misgeld, T., & Godinho, L. (2021) · Current Biology · doi:10.1016/j.cub.2021.08.049 · Cited by 16
Notch Signaling Regulates Muscle Stem Cell Homeostasis and Regeneration in a Teleost Fish
Sultan, S. H. A., Dyer, C., & Knight, R. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.726281 · Cited by 16
Cheng, Y., Chiang, M., Shih, H., Ma, T., Yeh, T., Huang, Y.-C., Lin, C., & Lin, S. (2014) · Developmental Biology · doi:10.1016/j.ydbio.2014.10.018 · Cited by 16
Luque-Molina, I., Shi, Y., Abdullah, Y., Monaco, S., Hölzl‐Wenig, G., Mandl, C., & Ciccolini, F. (2019) · Stem Cell Reports · doi:10.1016/j.stemcr.2019.05.004 · Cited by 15
“To test this possibility, we blocked endogenous NOTCH signaling by injecting the g-secretase inhibitor DAPT (N-[N-(3,5-difluorophenacetyl)L-alanyl]-S-phenylglycine t-butyl ester) (Geling et al., 2002) in the lateral ventricle of Tlx / mice.”
MethodDifferential gene regulation in DAPT-treated Hydra reveals candidate direct Notch signalling targets
Moneer, J., Siebert, S., Krebs, S., Cazet, J. F., Prexl, A., Pan, Q., Juliano, C. E., & Böttger, A. (2021) · Journal of Cell Science · doi:10.1242/jcs.258768 · Cited by 13
Notch Signalling Is Required for the Formation of Structurally Stable Muscle Fibres in Zebrafish
Pascoal, S., de Lima, J. E., Leslie, J. D., Hughes, S. M., & Saúde, L. (2013) · PLoS ONE · doi:10.1371/journal.pone.0068021 · Cited by 16
“To examine the importance of Notch signalling at developmental stages closer to the time of fin formation, we made use of a known c-secretase inhibitor drug called DAPT to fully block Notch signalling in a time-controlled manner [30].”
MethodModelling Delta-Notch perturbations during zebrafish somitogenesis
Murray, P. J., Maini, P. K., & Baker, R. E. (2012) · Developmental Biology · doi:10.1016/j.ydbio.2012.10.014 · Cited by 16
Nicastrin Deficiency Induces Tyrosinase-Dependent Depigmentation and Skin Inflammation
Hsu, C.-H., Liou, G., & Jiang, Y. (2019) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2019.07.702 · Cited by 16
“(b) Non-genotyped offspring from heterozygous nicastrinhi1384 carriers show severe depigmentation when treated with 25 mM DAPT.”
MethodInfluentialIshimatsu, K., Horikawa, K., & Takeda, H. (2007) · Developmental Dynamics · doi:10.1002/dvdy.21139 · Cited by 16
“Significantly, this is observed in zebrafish embryos whereby the synchronous oscillation of her1 is easily disrupted after brief treatment with DAPT (Geling et al., 2002), a gamma-secretase inhibitor that reduces Notch activity (Fig.”
BackgroundLi, A., Muenst, S. E., Hoffman, J., Starck, L., Sarem, M., Fischer, A., Hütter, G., & Shastri, V. P. (2022) · Communications Biology · doi:10.1038/s42003-022-04236-5 · Cited by 19
Nikolakopoulou, A. M., Georgakopoulos, A., & Robakis, N. K. R. K. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.02.028 · Cited by 15
“To this end, we used the γ-secretase inhibitor DAPT extensively used to study γ-secretase function (30, 31).”
MethodSoto, R. A., Najia, M. A. T., Hachimi, M., Frame, J. M., Yette, G. A., da Rocha, E. L., Stankunas, K., Daley, G. Q., & North, T. E. (2021) · Stem Cell Reports · doi:10.1016/j.stemcr.2021.05.014 · Cited by 15
Webb, K. J., Coolen, M., Gloeckner, C. J., Stigloher, C., Bahn, B., Topp, S., Ueffing, M., & Bally‐Cuif, L. (2011) · BMC Developmental Biology · doi:10.1186/1471-213x-11-27 · Cited by 15
“As anticipated from previous studies [33], DAPT treatment increased the amount of neurog1-positive cells within each proneural cluster (Figure 6G-H>’) (79% of cases, n = 19).”
MethodResultSelf-citationNotch-regulated perineurium development from zebrafish spinal cord
Kim, H. H., Kim, S., Chung, A.-Y., Bae, Y., Hibi, M., Lim, C. S., & Park, H. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2008.10.072 · Cited by 15
The NOTCH pathway contributes to cell fate decision in myelopoiesis
Bugeon, L., Taylor, H. B., Progatzky, F., Lin, M. I., Ellis, C. D., Welsh, N. J., Smith, E. J., Vargesson, N., Gray, C., Renshaw, S. A., et al. (2011) · Haematologica · doi:10.3324/haematol.2011.044115 · Cited by 15
Efficient four‐drug cocktail therapy targeting amyloid‐β peptide for Alzheimer's disease
Asai, M., Iwata, N., Tomita, T., Iwatsubo, T., Ishiura, S., Saido, T. C., & Maruyama, K. (2010) · Journal of Neuroscience Research · doi:10.1002/jnr.22503 · Cited by 15
“proteins other than APP as an adverse effect (De Strooper et al., 1999; Geling et al., 2002; Wong et al., 2004).”
BackgroundInfluentialInhibition of Notch Signaling Protects Mouse Lung Against Zymosan-Induced Injury
Han, H., Gong, G., Bai, X., Lin, Y., Sun, J., Wang, W., Zhao, Y., Yang, L., Wang, X., Zhang, Z., et al. (2013) · Shock · doi:10.1097/shk.0b013e3182a102e5 · Cited by 14
Zebrafish phenotypic screen identifies novel Notch antagonists
Velaithan, V., Okuda, K. S., Ng, M. F., Samat, N., Leong, S. W., Faudzi, S. M. M., Abas, F., Shaari, K., Cheong, S. C., Tan, P. J., et al. (2017) · Investigational New Drugs · doi:10.1007/s10637-016-0423-y · Cited by 14
Modulators and Inhibitors of γ- and β-Secretases
Schmidt, B., Baumann, S., Narlawar, R., Braun, H. A., & Larbig, G. (2006) · Neurodegenerative Diseases · doi:10.1159/000095269 · Cited by 14
“DAPT has demonstrated robust efficacy in vivoat relatively high doses. Several preclinical studies revealed in vivo toxicity, because DAPT affects the Notch pathway at higher levels (100- to 1,000-fold) [”
BackgroundVaccines for conformational disorders
Sadowski, M. J., & Wısnıewskı, T. (2004) · Expert Review of Vaccines · doi:10.1586/14760584.3.3.279 · Cited by 14
Luminescent and fluorescent triple reporter plasmid constructs for Wnt, Hedgehog and Notch pathway
Maier, J., Elmenofi, S., Taschauer, A., Anton, M., Sami, H., & Ogris, M. (2019) · PLoS ONE · doi:10.1371/journal.pone.0226570 · Cited by 13
Su, F., Zhu, S., Ruan, J., Muftuoglu, Y., Zhang, L., & Yuan, Q. (2015) · Oncotarget · doi:10.18632/oncotarget.6769 · Cited by 13
“…HER2-overexpressing cells, we studied the effect of combining RY10-4 treatment with DAPT, a highly specific γ-secretase inhibitor that blocks Notch endoprotrolysis [20]), on cell viability using two HER2-positive cell lines (SKBR3 and BT-474) and two HER2-negative cell lines (MDA-MB-231 and MCF-7).”
Itoh, N., Okochi, M., Tagami, S., Nishitomi, K., Nakayama, T., Yanagida, K., Fukumori, A., Jiang, J., Mori, K., Hosono, M., et al. (2009) · Neurodegenerative Diseases · doi:10.1159/000236902 · Cited by 13
Self-citationLu, J., Zhang, J., Kim, K., Case, T. C., Matusik, R. J., Chen, Y., Wolfe, M. S., Nopparat, J., & Lu, Q. (2010) · Molecular Cancer · doi:10.1186/1476-4598-9-304 · Cited by 13
“These results are consistent with previously reported functions of Hes1 and δ-catenin and support a role of Hes1 suppression and δ-catenin expression in neuroendocrine tumor progression [21-23].”
ResultCell heterogeneity and fate bistability drive tissue patterning during intestinal regenerationPreprint
Schwayer, C., Barbiero, S., Brückner, D. B., Baader, C., Repina, N. A., Diaz, O. E., Meylan, L. C., Kalck, V., Suppinger, S., Yang, Q., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.01.14.632683 · Cited by 13
Uncovering Notch pathway in the parasitic flatworm Schistosoma mansoni
Magalhães, L. G., Morais, E. R., Machado, C. B., Gomes, M. D. S., Cabral, F. J., de Souza, J. A. S., Soares, C. S., de Sá, R. G., Castro‐Borges, W., & Rodrigues, V. (2016) · Parasitology Research · doi:10.1007/s00436-016-5161-8 · Cited by 12
The role of Niemann-Pick type C2 in zebrafish embryonic development
Tseng, W.-C., Escauriza, A. J. J., Tsai‐Morris, C., Feldman, B., Dale, R., Wassif, C. A., & Porter, F. D. (2021) · Development · doi:10.1242/dev.194258 · Cited by 12
Enhanced Osteogenic Differentiation of Pluripotent Stem Cells via γ-Secretase Inhibition
Helmi, S. A., Rohani, L., Zaher, A. R., Hawary, Y. M. E., & Rancourt, D. E. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22105215 · Cited by 12
Castro, M. A., Parson, K. F., Beg, I., Wilkinson, M. C., Nurmakova, K., Levesque, I., Voehler, M., Wolfe, M. S., Ruotolo, B. T., & Sanders, C. R. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.101792 · Cited by 13
Dyer, C., Linker, C., Graham, A., & Knight, R. (2014) · Developmental Dynamics · doi:10.1002/dvdy.24184 · Cited by 12
“This was achieved by treating embryos with DAPT, an inhibitor of gamma-secretase, resulting in an inhibition of active Notch signalling (Geling et al., 2002).”
MethodNotch Signaling and Maintenance of SOX2 Expression in Rat Anterior Pituitary Cells
Batchuluun, K., Azuma, M., Fujiwara, K., Yashiro, T., & Kikuchi, M. (2017) · ACTA HISTOCHEMICA ET CYTOCHEMICA · doi:10.1267/ahc.17002 · Cited by 12
NOTCH signalling – a core regulator of bile duct disease?
Lyons, A. M., & Boulter, L. (2023) · Disease Models & Mechanisms · doi:10.1242/dmm.050231 · Cited by 12
A Pentacyclic Triterpene from Ligustrum lucidum Targets γ-Secretase
Luo, W., Ip, F. C. F., Fu, G., Cheung, K., Tian, Y., Hu, Y., Sinha, A., Cheng, E. Y. L., Wu, X., Bustos, V., et al. (2020) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.0c00389 · Cited by 11
Gassman, A., Hao, L. T., Bhoite, L. T., Bradford, C. L., Chien, C.-B., Beattie, C. E., & Manfredi, J. P. (2013) · PLoS ONE · doi:10.1371/journal.pone.0074325 · Cited by 11
“In contrast, treatment with 32 mM DAPT, which has been shown to alter Notch processing in zebrafish [73], consistently disrupted the regularity of somite boundaries.”
ResultUpscaling of hiPS Cell–Derived Neurons for High-Throughput Screening
Traub, S., Stahl, H. F., Rosenbrock, H., Simon, E., & Heilker, R. (2016) · SLAS DISCOVERY · doi:10.1177/1087057116678161 · Cited by 11
“pharmacologically blocked Notch signaling by the γ-secretase inhibitor DAPT, which had previously been demonstrated to produce identical effects as Notch loss-of-function mutations.(26) In a combination of growth factor withdrawal and inhibition of Notch signaling, they elegantly shortened the neuronal and synaptic ma…”
BackgroundChapouton, P., & Godinho, L. (2010) · Methods in cell biology · doi:10.1016/b978-0-12-384892-5.00004-9 · Cited by 11
Reynolds, E., Himmelwright, R., Sanginiti, C., & Pfaffmann, J. O. (2019) · BMC Systems Biology · doi:10.1186/s12918-018-0672-9 · Cited by 11
“There are chemical inhibitors of the proteases involved in the cleavage step that could be used at varying dosages to produce alterations in the efficiency of the process [37, 38].”
BackgroundHajdú, M., Kopper, L., & Sebestyén, A. (2009) · Scandinavian Journal of Immunology · doi:10.1111/j.1365-3083.2009.02346.x · Cited by 11
Yang, T., Arslanova, D., Xu, X., Li, Y., & Xia, W. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06681.x · Cited by 11
“These phenotypes can be replicated in zebrafish treated with a potent GSI, DAPT (N-[N-(3,5difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butyl ester), at the late blastula stage (Geling et al. 2002).”
BackgroundRusdi, N. ‘., Kue, C. S., Yu, K.-X., Lau, B. F., Chung, L. Y., & Kiew, L. V. (2019) · Natural Product Communications · doi:10.1177/1934578x19857909 · Cited by 11
Li, C., Huang, S., Zhou, W., Xie, Z., Xie, S., & Li, M. (2022) · Neurochemical Research · doi:10.1007/s11064-022-03558-4 · Cited by 10
“DAPT is a new type of gamma secretase inhibitor, which has been widely used in the study of Notch signaling pathway and can effectively inhibit the expression of Hes1 gene [14].”
BackgroundLara‐Ramírez, R., Gonzalez, C. P., Anselmi, C., Patthey, C., & Shimeld, S. M. (2018) · Development · doi:10.1242/dev.166595 · Cited by 10
“Neither, as would be predicted from comparison with jawed vertebrates, is there a general, relatively homogenous, upregulation of expression (Geling et al., 2002; Nornes et al., 2008; Yang et al., 2006).”
BackgroundMethodInfluentialKobayashi, M., Chijimatsu, R., Hart, D. A., Hamamoto, S., Jacob, G., Yano, F., Saito, T., Shimomura, K., Ando, W., Chung, U., et al. (2020) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.3149 · Cited by 10
Perspectives on the discovery of NOTCH2‐specific inhibitors
Dobranowski, P., Ban, F., Contreras‐Sanz, A., Cherkasov, A. R., & Black, P. C. (2017) · Chemical Biology & Drug Design · doi:10.1111/cbdd.13132 · Cited by 9
Jannuzzi, G. P., de Almeida, J. R. F., dos Santos, S. S., de Almeida, S. R., & Ferreira, K. S. (2018) · Mycopathologia · doi:10.1007/s11046-018-0276-3 · Cited by 9
Kim, C., Lee, S.-M., Ko, E., Go, R., Jeung, E., Kim, M., & Choi, K. (2020) · Reproductive Toxicology · doi:10.1016/j.reprotox.2020.05.010 · Cited by 9
Lin, L.-F., Liao, M., Xue, X., Zhang, W., Yan, L., Cai, L., Zhou, X., Zhou, X., & Luo, H. (2012) · Neuroscience Bulletin · doi:10.1007/s12264-012-1287-6 · Cited by 10
“[80] Geling A, Steiner H, Willem M, Bally-Cuif L, Haass C.”
Ilyanassa Notch signaling implicated in dynamic signaling between all three germ layers
Gharbiah, M., Nakamoto, A., Johnson, A. B., Lambert, J. D., & Nagy, L. M. (2014) · The International Journal of Developmental Biology · doi:10.1387/ijdb.140149ln · Cited by 9
“…frequently used to block N signaling in many different systems and is known to phenocopy disruption of N function produced through mutation or RNAi (Geling et al., 2002; Micchelli et al., 2003; Chen et al., 2006; Fujimaki et al., 2006; Gal et al., 2006; Kitzmann et al., 2006; Li et al., 2006;…”
BackgroundInfluentialAbbas, O. L., Özatik, O., Terzi, Y. K., Özatik, F. Y., Nar, R., & Saltoğlu, G. T. (2017) · Journal of Burn Care & Research · doi:10.1097/bcr.0000000000000522 · Cited by 9
Tnpo3 enables EBF1 function in conditions of antagonistic Notch signalingPreprint
Bayer, M., Boller, S., Ramamoorthy, S., Zolotarev, N., Cauchy, P., Iwanami, N., Mittler, G., Boehm, T. L. J., & Grosschedl, R. (2022) · Genes & Development · doi:10.1101/gad.349696.122 · Cited by 9
“This small molecule inhibits the proteolytic cleavage of the Notch1 receptor and release of the NICD into the nucleus (Geling et al. 2002).”
Zhang, W., Li, Y., Chen, S., Zhang, C., Chen, L., & Peng, G. (2021) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2021.08.019 · Cited by 9
Lecanu, L., & Papadopoulos, V. (2007) · Recent Patents on CNS Drug Discovery · doi:10.2174/157488907780832715 · Cited by 8
Identifying Direct Notch Transcriptional Targets Using the GSI-Washout Assay
Bailis, W., Yashiro–Ohtani, Y., & Pear, W. S. (2014) · Methods in molecular biology · doi:10.1007/978-1-4939-1139-4_19 · Cited by 8
Prenatal diagnosis of congenital rubella infection and ultrasonography: a preliminary study.
Migliucci, A., Fraja, D. D., Sarno, L., Acampora, E., Mazzarelli, L. L., Quaglia, F., Milanes, G. M., Buffolano, W., Napolitano, R., Simioli, S., et al. (2011) · PubMed · Cited by 8
Chemical approaches to angiogenesis.
Chan, J., & Serluca, F. (2004) · Methods in Cell Biology · doi:10.1016/s0091-679x(04)76021-5 · Cited by 11
Metadata
- Authors
- Geling, A., Steiner, H., Willem, M., Bally‐Cuif, L., & Haass, C.
- Affiliations
- Technical University of Munich (DE)
- Adolf-Butenandt-Institut für Physiologische Chemie, Physikalische Biochemie und Zellbiologie (DE)
- Venue
- The EMBO Reports
- Published
- 2002-07-01
- Volume
- 3
- Issue
- 7
- Pages
- 688-694
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- OpenAlex
- W2082694975
- Cited by
- 497
- References
- 56
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 12 · 2023: 7 · 2022: 13 · 2021: 15 · 2020: 14 · 2019: 27 · 2018: 13 · 2017: 17 · 2016: 25 · 2015: 16 · 2014: 19 · 2013: 28 · 2012: 34
- FWCI
- 11.57
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- EMBO Reports (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
- Keywords
- gamma-secretase inhibitors, Notch signaling, presenilin, amyloid-beta, Alzheimer's disease, neurogenesis, zebrafish embryos, embryonic development, off-target effects, cell fate determination, adverse drug reactions
- MeSH terms
- Alzheimer Disease, Animals, Cell Line, Enzyme Inhibitors, gamma-Aminobutyric Acid, Humans, Membrane Proteins, Microinjections, Endopeptidases, Phenotype, RNA, Messenger, Triglycerides, Zebrafish, Signal Transduction, Aspartic Acid Endopeptidases, Amyloid beta-Protein Precursor, In Situ Hybridization, Body Patterning, Receptors, Notch, Presenilin-1, Amyloid Precursor Protein Secretases
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