Search

Your search keyword '"Dehairs, Jonas"' showing total 219 results
Start Over Author "Dehairs, Jonas"
219 results on '"Dehairs, Jonas"'

5. Pharmacological induction of membrane lipid poly-unsaturation sensitizes melanoma to ROS inducers and overcomes acquired resistance to targeted therapy

Author

Talebi, Ali, de Laat, Vincent, Spotbeen, Xander, Dehairs, Jonas, Rambow, Florian, Rogiers, Aljosja, Vanderhoydonc, Frank, Rizotto, Lara, Planque, Mélanie, Doglioni, Ginevra, Motamedi, Sahar, Nittner, David, Roskams, Tania, Agostinis, Patrizia, Bechter, Oliver, Boecxstaens, Veerle, Garmyn, Marjan, O’Farrell, Marie, Wagman, Alan, Kemble, George, Leucci, Eleonora, Fendt, Sarah-Maria, Marine, Jean-Christophe, and Swinnen, Johannes V.

Published
2023
Full Text
View/download PDF

6. Fatty acid desaturation by stearoyl-CoA desaturase-1 controls regulatory T cell differentiation and autoimmunity

Author

Grajchen, Elien, Loix, Melanie, Baeten, Paulien, Côrte-Real, Beatriz F., Hamad, Ibrahim, Vanherle, Sam, Haidar, Mansour, Dehairs, Jonas, Broos, Jelle Y., Ntambi, James M., Zimmermann, Robert, Breinbauer, Rolf, Stinissen, Piet, Hellings, Niels, Verberk, Sanne G. S., Kooij, Gijs, Giera, Martin, Swinnen, Johannes V., Broux, Bieke, Kleinewietfeld, Markus, Hendriks, Jerome J. A., and Bogie, Jeroen F. J.

Published
2023
Full Text
View/download PDF

8. Peroxisome disruption alters lipid metabolism and potentiates antitumor response with MAPK-targeted therapy in melanoma

Author

Huang, Fan, Cai, Feiyang, Dahabieh, Michael S., Gunawardena, Kshemaka, Talebi, Ali, Dehairs, Jonas, El-Turk, Farah, Park, Jae Yeon, Li, Mengqi, Goncalves, Christophe, Gagnon, Natascha, Su, Jie, LaPierre, Judith H., Gaub, Perrine, Joyal, Jean-Sebastien, Mitchell, John J., Swinnen, Johannes V., Miller, Wilson H., Jr., and del Rincon, Sonia V.

Subjects
Cellulose -- Physiological aspects, Ceramides -- Physiological aspects, Biosynthesis -- Physiological aspects, Vemurafenib -- Physiological aspects, Cancer -- Care and treatment, Apoptosis -- Physiological aspects, Melanoma -- Development and progression, Health care industry
Abstract

Melanomas reprogram their metabolism to rapidly adapt to therapy-induced stress conditions, allowing them to persist and ultimately develop resistance. We report that a subpopulation of melanoma cells tolerate MAPK pathway inhibitors (MAPKis) through a concerted metabolic reprogramming mediated by peroxisomes and UDP-glucose ceramide glycosyltransferase (UGCG). Compromising peroxisome biogenesis, by repressing PEX3 expression, potentiated the proapoptotic effects of MAPKis via an induction of ceramides, an effect limited by UGCG-mediated ceramide metabolism. Cotargeting PEX3 and UGCG selectively eliminated a subset of metabolically active, drug-tolerant [CD36.sup.+] melanoma persister cells, thereby sensitizing melanoma to MAPKis and delaying resistance. Increased levels of peroxisomal genes and UGCG were found in patient-derived MAPKi-relapsed melanomas, and simultaneously inhibiting PEX3 and UGCG restored MAPKi sensitivity in multiple models of therapy resistance. Finally, combination therapy consisting of a newly identified inhibitor of the PEX3PEX19 interaction, a UGCG inhibitor, and MAPKis demonstrated potent antitumor activity in preclinical melanoma models, thus representing a promising approach for melanoma treatment., Introduction Melanoma is the deadliest form of skin cancer. Current treatments for patients with metastatic melanoma include therapies that target the MAPK pathway (BRAF and MEK inhibitors) and immunotherapies targeting [...]

Published
2023
Full Text
View/download PDF

9. PMP22 duplication dysregulates lipid homeostasis and plasma membrane organization in developing human Schwann cells

Author

Prior, Robert, primary, Silva, Alessio, additional, Vangansewinkel, Tim, additional, Idkowiak, Jakub, additional, Tharkeshwar, Arun Kumar, additional, Hellings, Tom P, additional, Michailidou, Iliana, additional, Vreijling, Jeroen, additional, Loos, Maarten, additional, Koopmans, Bastijn, additional, Vlek, Nina, additional, Agaser, Cedrick, additional, Kuipers, Thomas B, additional, Michiels, Christine, additional, Rossaert, Elisabeth, additional, Verschoren, Stijn, additional, Vermeire, Wendy, additional, de Laat, Vincent, additional, Dehairs, Jonas, additional, Eggermont, Kristel, additional, van den Biggelaar, Diede, additional, Bademosi, Adekunle T, additional, Meunier, Frederic A, additional, vandeVen, Martin, additional, Van Damme, Philip, additional, Mei, Hailiang, additional, Swinnen, Johannes V, additional, Lambrichts, Ivo, additional, Baas, Frank, additional, Fluiter, Kees, additional, Wolfs, Esther, additional, and Van Den Bosch, Ludo, additional

Published
2024
Full Text
View/download PDF

13. Circulating Lipid Profiles Associated With Resistance to Androgen Deprivation Therapy in Localized Prostate Cancer.

Author

Lin, Hui-Ming, Yang, Xiaoyu, Centenera, Margaret M., Huynh, Kevin, Giles, Corey, Dehairs, Jonas, Swinnen, Johannes V., Hoy, Andrew J., Meikle, Peter J., Butler, Lisa M., Taplin, Mary-Ellen, and Horvath, Lisa G.

Subjects
BLOOD lipids, ANDROGEN receptors, ANDROGEN deprivation therapy, FREE fatty acids, RADICAL prostatectomy, PROSTATE cancer
Abstract

PURPOSE: Intense androgen deprivation therapy (ADT) with androgen receptor pathway inhibitors (ARPIs) before radical prostatectomy (RP) produced favorable pathologic responses in approximately 20% of patients. The molecular reason for the low rate of response remains unclear. Lipid metabolism is known to influence androgen receptor signaling and ARPI efficacy. The aim of the study was to identify circulating lipid profiles associated with ADT/ARPI resistance in localized prostate cancer. MATERIALS AND METHODS: Two independent experimental approaches were used. Experiment 1: Post hoc analysis of the association between plasma lipidomic profiles and ADT/ARPI response was performed on patients (n = 104) from two phase II trials of neoadjuvant ADT/ARPI. Response to ADT/ARPI was defined by pathologic response. Experiment 2: Patient-derived tumor explants from RP (n = 105) were cultured in enzalutamide for 48 hours. Explant response to enzalutamide was evaluated against pre-RP plasma lipidomic profiles (n = 105) and prostate tissue lipidomic profiles (n = 36). Response was defined by Ki67 (cell proliferation marker) fold difference between enzalutamide and vehicle-treated explants. In both experiments, associations between lipid profiles and ADT/ARPI response were analyzed by latent class analysis. RESULTS: Pretreatment plasma lipid profiles classified each experimental cohort into two groups with differences in ADT/ARPI response rates. The response rates of the groups were 9.6% versus 29% in experiment 1 (chi-squared test P =.012) and 49% versus 70% in experiment 2 (chi-squared test P =.037). In both experiments, the group with a higher incidence of ADT/ARPI resistance had higher plasma levels of sphingomyelin, glycosylceramides, free fatty acids, acylcarnitines, cholesterol esters, and alkyl/alkenyl-phosphatidylcholine and lower plasma levels of triacylglycerols, diacylglycerols, and phosphoethanolamine (t-test P <.05). CONCLUSION: Pretreatment circulating lipid profiles are associated with ADT/ARPI resistance in localized cancer in both human cohorts and explant models. Plasma lipids are associated with response to neoadjuvant anti-androgen in localized prostate cancer. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

14. Cis-vaccenic acid is a key product of stearoyl-CoA desaturase 1 and a critical oncogenic factor in prostate cancer

Author

Scott, Julia S, primary, Young, Reuben SE, additional, Quek, Lake-Ee, additional, Miller, Deanna C, additional, Evergren, Emma S, additional, Dehairs, Jonas, additional, Johnson, Ian RD, additional, Brooks, Doug A, additional, Loda, Massimo, additional, Hoy, Andrew J, additional, Blanksby, Stephen J, additional, Swinnen, Johannes V, additional, Nassar, Zeyad D, additional, and Butler, Lisa M, additional

Published
2024
Full Text
View/download PDF

15. Regulatory T cell differentiation is controlled by αKG-induced alterations in mitochondrial metabolism and lipid homeostasis

Author

Matias, Maria I., Yong, Carmen S., Foroushani, Amir, Goldsmith, Chloe, Mongellaz, Cédric, Sezgin, Erdinc, Levental, Kandice R., Talebi, Ali, Perrault, Julie, Rivière, Anais, Dehairs, Jonas, Delos, Océane, Bertand-Michel, Justine, Portais, Jean-Charles, Wong, Madeline, Marie, Julien C., Kelekar, Ameeta, Kinet, Sandrina, Zimmermann, Valérie S., Levental, Ilya, Yvan-Charvet, Laurent, Swinnen, Johannes V., Muljo, Stefan A., Hernandez-Vargas, Hector, Tardito, Saverio, Taylor, Naomi, and Dardalhon, Valérie

Published
2021
Full Text
View/download PDF

18. Extracellular vesicle‐associated cholesterol supports the regenerative functions of macrophages in the brain

Author

Vanherle, Sam, primary, Guns, Jeroen, additional, Loix, Melanie, additional, Mingneau, Fleur, additional, Dierckx, Tess, additional, Wouters, Flore, additional, Kuipers, Koen, additional, Vangansewinkel, Tim, additional, Wolfs, Esther, additional, Lins, Paula Pincela, additional, Bronckaers, Annelies, additional, Lambrichts, Ivo, additional, Dehairs, Jonas, additional, Swinnen, Johannes V., additional, Verberk, Sanne G. S., additional, Haidar, Mansour, additional, Hendriks, Jerome J. A., additional, and Bogie, Jeroen F. J., additional

Published
2023
Full Text
View/download PDF

19. Fatty acid elongation by ELOVL6 hampers remyelination by promoting inflammatory foam cell formation during demyelination

Author

Garcia Corrales, Aida V., primary, Verberk, Sanne G. S., additional, Haidar, Mansour, additional, Grajchen, Elien, additional, Dehairs, Jonas, additional, Vanherle, Sam, additional, Loix, Melanie, additional, Weytjens, Tine, additional, Gervois, Pascal, additional, Matsuzaka, Takashi, additional, Lambrichts, Ivo, additional, Swinnen, Johannes V., additional, Bogie, Jeroen F. J., additional, and Hendriks, Jerome J. A., additional

Published
2023
Full Text
View/download PDF

20. Integration of Multiple Spatial-Omics Modalities Reveals Unique Insights into Molecular Heterogeneity of Prostate Cancer

Author

Zhang, Wanqiu, primary, Spotbeen, Xander, additional, Vanuytven, Sebastiaan, additional, Kint, Sam, additional, Sarretto, Tassiani, additional, Socciarelli, Fabio, additional, Vandereyken, Katy, additional, Dehairs, Jonas, additional, Idkowiak, Jakub, additional, Wouters, David, additional, Alvira Larizgoitia, Jose Ignacio, additional, Partel, Gabriele, additional, Ly, Alice, additional, de Laat, Vincent, additional, Q. Mantas, Maria Jose, additional, Gevaert, Thomas, additional, Devlies, Wout, additional, Mah, Chui Yan, additional, Butler, Lisa M, additional, Loda, Massimo, additional, Joniau, Steven, additional, De Moor, Bart, additional, Sifrim, Alejandro, additional, Ellis, Shane R., additional, Voet, Thierry, additional, Claesen, Marc, additional, Verbeeck, Nico, additional, and Swinnen, Johannes V., additional

Published
2023
Full Text
View/download PDF

21. Data from C/EBPα Confers Dependence to Fatty Acid Anabolic Pathways and Vulnerability to Lipid Oxidative Stress–Induced Ferroptosis in FLT3-Mutant Leukemia

Author

Sabatier, Marie, primary, Birsen, Rudy, primary, Lauture, Laura, primary, Mouche, Sarah, primary, Angelino, Paolo, primary, Dehairs, Jonas, primary, Goupille, Léa, primary, Boussaid, Ismael, primary, Heiblig, Maël, primary, Boet, Emeline, primary, Sahal, Ambrine, primary, Saland, Estelle, primary, Santos, Juliana C., primary, Armengol, Marc, primary, Fernández-Serrano, Miranda, primary, Farge, Thomas, primary, Cognet, Guillaume, primary, Simonetta, Federico, primary, Pignon, Corentin, primary, Graffeuil, Antoine, primary, Mazzotti, Céline, primary, Avet-Loiseau, Hervé, primary, Delos, Océane, primary, Bertrand-Michel, Justine, primary, Chedru, Amélie, primary, Dembitz, Vilma, primary, Gallipoli, Paolo, primary, Anstee, Natasha S., primary, Loo, Sun, primary, Wei, Andrew H., primary, Carroll, Martin, primary, Goubard, Armelle, primary, Castellano, Rémy, primary, Collette, Yves, primary, Vergez, François, primary, Mansat-De Mas, Véronique, primary, Bertoli, Sarah, primary, Tavitian, Suzanne, primary, Picard, Muriel, primary, Récher, Christian, primary, Bourges-Abella, Nathalie, primary, Granat, Fanny, primary, Kosmider, Olivier, primary, Sujobert, Pierre, primary, Colsch, Benoit, primary, Joffre, Carine, primary, Stuani, Lucille, primary, Swinnen, Johannes V., primary, Guillou, Hervé, primary, Roué, Gael, primary, Hakim, Nawad, primary, Dejean, Anne S., primary, Tsantoulis, Petros, primary, Larrue, Clément, primary, Bouscary, Didier, primary, Tamburini, Jerome, primary, and Sarry, Jean-Emmanuel, primary

Published
2023
Full Text
View/download PDF

22. Supplementary Information v.2 from C/EBPα Confers Dependence to Fatty Acid Anabolic Pathways and Vulnerability to Lipid Oxidative Stress–Induced Ferroptosis in FLT3-Mutant Leukemia

Author

Sabatier, Marie, primary, Birsen, Rudy, primary, Lauture, Laura, primary, Mouche, Sarah, primary, Angelino, Paolo, primary, Dehairs, Jonas, primary, Goupille, Léa, primary, Boussaid, Ismael, primary, Heiblig, Maël, primary, Boet, Emeline, primary, Sahal, Ambrine, primary, Saland, Estelle, primary, Santos, Juliana C., primary, Armengol, Marc, primary, Fernández-Serrano, Miranda, primary, Farge, Thomas, primary, Cognet, Guillaume, primary, Simonetta, Federico, primary, Pignon, Corentin, primary, Graffeuil, Antoine, primary, Mazzotti, Céline, primary, Avet-Loiseau, Hervé, primary, Delos, Océane, primary, Bertrand-Michel, Justine, primary, Chedru, Amélie, primary, Dembitz, Vilma, primary, Gallipoli, Paolo, primary, Anstee, Natasha S., primary, Loo, Sun, primary, Wei, Andrew H., primary, Carroll, Martin, primary, Goubard, Armelle, primary, Castellano, Rémy, primary, Collette, Yves, primary, Vergez, François, primary, Mansat-De Mas, Véronique, primary, Bertoli, Sarah, primary, Tavitian, Suzanne, primary, Picard, Muriel, primary, Récher, Christian, primary, Bourges-Abella, Nathalie, primary, Granat, Fanny, primary, Kosmider, Olivier, primary, Sujobert, Pierre, primary, Colsch, Benoit, primary, Joffre, Carine, primary, Stuani, Lucille, primary, Swinnen, Johannes V., primary, Guillou, Hervé, primary, Roué, Gael, primary, Hakim, Nawad, primary, Dejean, Anne S., primary, Tsantoulis, Petros, primary, Larrue, Clément, primary, Bouscary, Didier, primary, Tamburini, Jerome, primary, and Sarry, Jean-Emmanuel, primary

Published
2023
Full Text
View/download PDF

23. Supplementary Figures S1-S22 from C/EBPα Confers Dependence to Fatty Acid Anabolic Pathways and Vulnerability to Lipid Oxidative Stress–Induced Ferroptosis in FLT3-Mutant Leukemia

Author

Sabatier, Marie, primary, Birsen, Rudy, primary, Lauture, Laura, primary, Mouche, Sarah, primary, Angelino, Paolo, primary, Dehairs, Jonas, primary, Goupille, Léa, primary, Boussaid, Ismael, primary, Heiblig, Maël, primary, Boet, Emeline, primary, Sahal, Ambrine, primary, Saland, Estelle, primary, Santos, Juliana C., primary, Armengol, Marc, primary, Fernández-Serrano, Miranda, primary, Farge, Thomas, primary, Cognet, Guillaume, primary, Simonetta, Federico, primary, Pignon, Corentin, primary, Graffeuil, Antoine, primary, Mazzotti, Céline, primary, Avet-Loiseau, Hervé, primary, Delos, Océane, primary, Bertrand-Michel, Justine, primary, Chedru, Amélie, primary, Dembitz, Vilma, primary, Gallipoli, Paolo, primary, Anstee, Natasha S., primary, Loo, Sun, primary, Wei, Andrew H., primary, Carroll, Martin, primary, Goubard, Armelle, primary, Castellano, Rémy, primary, Collette, Yves, primary, Vergez, François, primary, Mansat-De Mas, Véronique, primary, Bertoli, Sarah, primary, Tavitian, Suzanne, primary, Picard, Muriel, primary, Récher, Christian, primary, Bourges-Abella, Nathalie, primary, Granat, Fanny, primary, Kosmider, Olivier, primary, Sujobert, Pierre, primary, Colsch, Benoit, primary, Joffre, Carine, primary, Stuani, Lucille, primary, Swinnen, Johannes V., primary, Guillou, Hervé, primary, Roué, Gael, primary, Hakim, Nawad, primary, Dejean, Anne S., primary, Tsantoulis, Petros, primary, Larrue, Clément, primary, Bouscary, Didier, primary, Tamburini, Jerome, primary, and Sarry, Jean-Emmanuel, primary

Published
2023
Full Text
View/download PDF

24. Supplementary Table S15 from C/EBPα Confers Dependence to Fatty Acid Anabolic Pathways and Vulnerability to Lipid Oxidative Stress–Induced Ferroptosis in FLT3-Mutant Leukemia

Author

Sabatier, Marie, primary, Birsen, Rudy, primary, Lauture, Laura, primary, Mouche, Sarah, primary, Angelino, Paolo, primary, Dehairs, Jonas, primary, Goupille, Léa, primary, Boussaid, Ismael, primary, Heiblig, Maël, primary, Boet, Emeline, primary, Sahal, Ambrine, primary, Saland, Estelle, primary, Santos, Juliana C., primary, Armengol, Marc, primary, Fernández-Serrano, Miranda, primary, Farge, Thomas, primary, Cognet, Guillaume, primary, Simonetta, Federico, primary, Pignon, Corentin, primary, Graffeuil, Antoine, primary, Mazzotti, Céline, primary, Avet-Loiseau, Hervé, primary, Delos, Océane, primary, Bertrand-Michel, Justine, primary, Chedru, Amélie, primary, Dembitz, Vilma, primary, Gallipoli, Paolo, primary, Anstee, Natasha S., primary, Loo, Sun, primary, Wei, Andrew H., primary, Carroll, Martin, primary, Goubard, Armelle, primary, Castellano, Rémy, primary, Collette, Yves, primary, Vergez, François, primary, Mansat-De Mas, Véronique, primary, Bertoli, Sarah, primary, Tavitian, Suzanne, primary, Picard, Muriel, primary, Récher, Christian, primary, Bourges-Abella, Nathalie, primary, Granat, Fanny, primary, Kosmider, Olivier, primary, Sujobert, Pierre, primary, Colsch, Benoit, primary, Joffre, Carine, primary, Stuani, Lucille, primary, Swinnen, Johannes V., primary, Guillou, Hervé, primary, Roué, Gael, primary, Hakim, Nawad, primary, Dejean, Anne S., primary, Tsantoulis, Petros, primary, Larrue, Clément, primary, Bouscary, Didier, primary, Tamburini, Jerome, primary, and Sarry, Jean-Emmanuel, primary

Published
2023
Full Text
View/download PDF

25. Evidence for an alternative fatty acid desaturation pathway increasing cancer plasticity

Author

Vriens, Kim, Christen, Stefan, Parik, Sweta, Broekaert, Dorien, Yoshinaga, Kazuaki, Talebi, Ali, and Dehairs, Jonas

Subjects
Cancer cells -- Physiological aspects -- Research, Cancer research, Fatty acid metabolism -- Research, Cancer, Fatty acids, Lung cancer, Tumors, Neurophysiology, Liver, Liver cancer, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Most tumours have an aberrantly activated lipid metabolism.sup.1,2 that enables them to synthesize, elongate and desaturate fatty acids to support proliferation. However, only particular subsets of cancer cells are sensitive to approaches that target fatty acid metabolism and, in particular, fatty acid desaturation.sup.3. This suggests that many cancer cells contain an unexplored plasticity in their fatty acid metabolism. Here we show that some cancer cells can exploit an alternative fatty acid desaturation pathway. We identify various cancer cell lines, mouse hepatocellular carcinomas, and primary human liver and lung carcinomas that desaturate palmitate to the unusual fatty acid sapienate to support membrane biosynthesis during proliferation. Accordingly, we found that sapienate biosynthesis enables cancer cells to bypass the known fatty acid desaturation pathway that is dependent on stearoyl-CoA desaturase. Thus, only by targeting both desaturation pathways is the in vitro and in vivo proliferation of cancer cells that synthesize sapienate impaired. Our discovery explains metabolic plasticity in fatty acid desaturation and constitutes an unexplored metabolic rewiring in cancers. In several human and mouse cancer cell lines and carcinomas, a sapienate biosynthesis pathway underpins metabolic plasticity by allowing these cells to bypass stearoyl-CoA desaturase-dependent fatty acid desaturation., Author(s): Kim Vriens [sup.1] [sup.2] , Stefan Christen [sup.1] [sup.2] , Sweta Parik [sup.1] [sup.2] [sup.3] [sup.4] , Dorien Broekaert [sup.1] [sup.2] , Kazuaki Yoshinaga [sup.5] [sup.6] , Ali Talebi [...]

Published
2019
Full Text
View/download PDF

26. Ceramide analog [18F]F-HPA-12 detects sphingolipid disbalance in the brain of Alzheimer’s disease transgenic mice by functioning as a metabolic probe

Author

Crivelli, Simone M., van Kruining, Daan, Luo, Qian, Stevens, Jo A. A., Giovagnoni, Caterina, Paulus, Andreas, Bauwens, Matthias, Berkes, Dusan, de Vries, Helga E., Mulder, Monique T., Walter, Jochen, Waelkens, Etienne, Derua, Rita, Swinnen, Johannes V., Dehairs, Jonas, Mottaghy, Felix M., Losen, Mario, Bieberich, Erhard, and Martinez-Martinez, Pilar

Published
2020
Full Text
View/download PDF

27. Altered Functionality of Lipoprotein(a) Impacts on Angiogenesis in Diabetic Retinopathy

Author

Shariatzadeh, Mahnaz, primary, Nagtzaam, Nicole M. A., additional, van Vark-van der Zee, Leonie, additional, van Holten-Neelen, Conny, additional, Verhoeven, Adrie J. M., additional, Dehairs, Jonas, additional, Swinnen, Johannes V., additional, Leijten, Frank, additional, ten Berge, Josianne C., additional, Ciriano, Jose P. Martinez, additional, Wong, King T., additional, Mulder, Monique, additional, Leenen, Pieter J. M., additional, and Dik, Willem A., additional

Published
2023
Full Text
View/download PDF

28. Abstract 1157: Uncovering a novel role of peroxisomal β-oxidation in advanced, treatment-resistant prostate cancer

Author

Mah, Chui Yan, primary, Nguyen, An D., additional, Niijima, Takuto, additional, Helm, Madison, additional, Dehairs, Jonas, additional, Ryan, Feargal J., additional, Ryan, Natalie, additional, Mills, Ian G., additional, Swinnen, Johannes V., additional, Lynn, David J., additional, Nassar, Zeyad D., additional, and Butler, Lisa M., additional

Published
2023
Full Text
View/download PDF

29. C/EBPα Confers Dependence to Fatty Acid Anabolic Pathways and Vulnerability to Lipid Oxidative Stress–Induced Ferroptosis inFLT3-Mutant Leukemia

Author

Sabatier, Marie, primary, Birsen, Rudy, additional, Lauture, Laura, additional, Mouche, Sarah, additional, Angelino, Paolo, additional, Dehairs, Jonas, additional, Goupille, Léa, additional, Boussaid, Ismael, additional, Heiblig, Maël, additional, Boet, Emeline, additional, Sahal, Ambrine, additional, Saland, Estelle, additional, Santos, Juliana C., additional, Armengol, Marc, additional, Fernández-Serrano, Miranda, additional, Farge, Thomas, additional, Cognet, Guillaume, additional, Simonetta, Federico, additional, Pignon, Corentin, additional, Graffeuil, Antoine, additional, Mazzotti, Céline, additional, Avet-Loiseau, Hervé, additional, Delos, Océane, additional, Bertrand-Michel, Justine, additional, Chedru, Amélie, additional, Dembitz, Vilma, additional, Gallipoli, Paolo, additional, Anstee, Natasha S., additional, Loo, Sun, additional, Wei, Andrew H., additional, Carroll, Martin, additional, Goubard, Armelle, additional, Castellano, Rémy, additional, Collette, Yves, additional, Vergez, François, additional, Mansat-De Mas, Véronique, additional, Bertoli, Sarah, additional, Tavitian, Suzanne, additional, Picard, Muriel, additional, Récher, Christian, additional, Bourges-Abella, Nathalie, additional, Granat, Fanny, additional, Kosmider, Olivier, additional, Sujobert, Pierre, additional, Colsch, Benoit, additional, Joffre, Carine, additional, Stuani, Lucille, additional, Swinnen, Johannes V., additional, Guillou, Hervé, additional, Roué, Gael, additional, Hakim, Nawad, additional, Dejean, Anne S., additional, Tsantoulis, Petros, additional, Larrue, Clément, additional, Bouscary, Didier, additional, Tamburini, Jerome, additional, and Sarry, Jean-Emmanuel, additional

Published
2023
Full Text
View/download PDF

30. Data from Lipidomic Profiling of Clinical Prostate Cancer Reveals Targetable Alterations in Membrane Lipid Composition

Author

Butler, Lisa M., primary, Mah, Chui Yan, primary, Machiels, Jelle, primary, Vincent, Andrew D., primary, Irani, Swati, primary, Mutuku, Shadrack M., primary, Spotbeen, Xander, primary, Bagadi, Muralidhararao, primary, Waltregny, David, primary, Moldovan, Max, primary, Dehairs, Jonas, primary, Vanderhoydonc, Frank, primary, Bloch, Katarzyna, primary, Das, Rajdeep, primary, Stahl, Jurgen, primary, Kench, James G., primary, Gevaert, Thomas, primary, Derua, Rita, primary, Waelkens, Etienne, primary, Nassar, Zeyad D., primary, Selth, Luke A., primary, Trim, Paul J., primary, Snel, Marten F., primary, Lynn, David J., primary, Tilley, Wayne D., primary, Horvath, Lisa G., primary, Centenera, Margaret M., primary, and Swinnen, Johannes V., primary

Published
2023
Full Text
View/download PDF

31. Supplementary Data from Fat Induces Glucose Metabolism in Nontransformed Liver Cells and Promotes Liver Tumorigenesis

Author

Broadfield, Lindsay A., primary, Duarte, João André Gonçalves, primary, Schmieder, Roberta, primary, Broekaert, Dorien, primary, Veys, Koen, primary, Planque, Mélanie, primary, Vriens, Kim, primary, Karasawa, Yasuaki, primary, Napolitano, Francesco, primary, Fujita, Suguru, primary, Fujii, Masashi, primary, Eto, Miki, primary, Holvoet, Bryan, primary, Vangoitsenhoven, Roman, primary, Fernandez-Garcia, Juan, primary, Van Elsen, Joke, primary, Dehairs, Jonas, primary, Zeng, Jia, primary, Dooley, James, primary, Rubio, Rebeca Alba, primary, van Pelt, Jos, primary, Grünewald, Thomas G.P., primary, Liston, Adrian, primary, Mathieu, Chantal, primary, Deroose, Christophe M., primary, Swinnen, Johannes V., primary, Lambrechts, Diether, primary, di Bernardo, Diego, primary, Kuroda, Shinya, primary, De Bock, Katrien, primary, and Fendt, Sarah-Maria, primary

Published
2023
Full Text
View/download PDF

32. Supplementary Data and Methods from Fat Induces Glucose Metabolism in Nontransformed Liver Cells and Promotes Liver Tumorigenesis

Author

Broadfield, Lindsay A., primary, Duarte, João André Gonçalves, primary, Schmieder, Roberta, primary, Broekaert, Dorien, primary, Veys, Koen, primary, Planque, Mélanie, primary, Vriens, Kim, primary, Karasawa, Yasuaki, primary, Napolitano, Francesco, primary, Fujita, Suguru, primary, Fujii, Masashi, primary, Eto, Miki, primary, Holvoet, Bryan, primary, Vangoitsenhoven, Roman, primary, Fernandez-Garcia, Juan, primary, Van Elsen, Joke, primary, Dehairs, Jonas, primary, Zeng, Jia, primary, Dooley, James, primary, Rubio, Rebeca Alba, primary, van Pelt, Jos, primary, Grünewald, Thomas G.P., primary, Liston, Adrian, primary, Mathieu, Chantal, primary, Deroose, Christophe M., primary, Swinnen, Johannes V., primary, Lambrechts, Diether, primary, di Bernardo, Diego, primary, Kuroda, Shinya, primary, De Bock, Katrien, primary, and Fendt, Sarah-Maria, primary

Published
2023
Full Text
View/download PDF

33. Supplementary Data from ELOVL5 Is a Critical and Targetable Fatty Acid Elongase in Prostate Cancer

Author

Centenera, Margaret M., primary, Scott, Julia S., primary, Machiels, Jelle, primary, Nassar, Zeyad D., primary, Miller, Deanna C., primary, Zinonos, Irene, primary, Dehairs, Jonas, primary, Burvenich, Ingrid J.G., primary, Zadra, Giorgia, primary, Chetta, Paolo M., primary, Bango, Clyde, primary, Evergren, Emma, primary, Ryan, Natalie K., primary, Gillis, Joanna L., primary, Mah, Chui Yan, primary, Tieu, Terence, primary, Hanson, Adrienne R., primary, Carelli, Ryan, primary, Bloch, Katarzyna, primary, Panagopoulos, Vasilios, primary, Waelkens, Etienne, primary, Derua, Rita, primary, Williams, Elizabeth D., primary, Evdokiou, Andreas, primary, Cifuentes-Rius, Anna, primary, Voelcker, Nicolas H., primary, Mills, Ian G., primary, Tilley, Wayne D., primary, Scott, Andrew M., primary, Loda, Massimo, primary, Selth, Luke A., primary, Swinnen, Johannes V., primary, and Butler, Lisa M., primary

Published
2023
Full Text
View/download PDF

34. Supplementary Table S1 from Lipidomic Profiling of Clinical Prostate Cancer Reveals Targetable Alterations in Membrane Lipid Composition

Author

Butler, Lisa M., primary, Mah, Chui Yan, primary, Machiels, Jelle, primary, Vincent, Andrew D., primary, Irani, Swati, primary, Mutuku, Shadrack M., primary, Spotbeen, Xander, primary, Bagadi, Muralidhararao, primary, Waltregny, David, primary, Moldovan, Max, primary, Dehairs, Jonas, primary, Vanderhoydonc, Frank, primary, Bloch, Katarzyna, primary, Das, Rajdeep, primary, Stahl, Jurgen, primary, Kench, James G., primary, Gevaert, Thomas, primary, Derua, Rita, primary, Waelkens, Etienne, primary, Nassar, Zeyad D., primary, Selth, Luke A., primary, Trim, Paul J., primary, Snel, Marten F., primary, Lynn, David J., primary, Tilley, Wayne D., primary, Horvath, Lisa G., primary, Centenera, Margaret M., primary, and Swinnen, Johannes V., primary

Published
2023
Full Text
View/download PDF

35. Data from ELOVL5 Is a Critical and Targetable Fatty Acid Elongase in Prostate Cancer

Author

Centenera, Margaret M., primary, Scott, Julia S., primary, Machiels, Jelle, primary, Nassar, Zeyad D., primary, Miller, Deanna C., primary, Zinonos, Irene, primary, Dehairs, Jonas, primary, Burvenich, Ingrid J.G., primary, Zadra, Giorgia, primary, Chetta, Paolo M., primary, Bango, Clyde, primary, Evergren, Emma, primary, Ryan, Natalie K., primary, Gillis, Joanna L., primary, Mah, Chui Yan, primary, Tieu, Terence, primary, Hanson, Adrienne R., primary, Carelli, Ryan, primary, Bloch, Katarzyna, primary, Panagopoulos, Vasilios, primary, Waelkens, Etienne, primary, Derua, Rita, primary, Williams, Elizabeth D., primary, Evdokiou, Andreas, primary, Cifuentes-Rius, Anna, primary, Voelcker, Nicolas H., primary, Mills, Ian G., primary, Tilley, Wayne D., primary, Scott, Andrew M., primary, Loda, Massimo, primary, Selth, Luke A., primary, Swinnen, Johannes V., primary, and Butler, Lisa M., primary

Published
2023
Full Text
View/download PDF

36. Data from Fat Induces Glucose Metabolism in Nontransformed Liver Cells and Promotes Liver Tumorigenesis

Author

Broadfield, Lindsay A., primary, Duarte, João André Gonçalves, primary, Schmieder, Roberta, primary, Broekaert, Dorien, primary, Veys, Koen, primary, Planque, Mélanie, primary, Vriens, Kim, primary, Karasawa, Yasuaki, primary, Napolitano, Francesco, primary, Fujita, Suguru, primary, Fujii, Masashi, primary, Eto, Miki, primary, Holvoet, Bryan, primary, Vangoitsenhoven, Roman, primary, Fernandez-Garcia, Juan, primary, Van Elsen, Joke, primary, Dehairs, Jonas, primary, Zeng, Jia, primary, Dooley, James, primary, Rubio, Rebeca Alba, primary, van Pelt, Jos, primary, Grünewald, Thomas G.P., primary, Liston, Adrian, primary, Mathieu, Chantal, primary, Deroose, Christophe M., primary, Swinnen, Johannes V., primary, Lambrechts, Diether, primary, di Bernardo, Diego, primary, Kuroda, Shinya, primary, De Bock, Katrien, primary, and Fendt, Sarah-Maria, primary

Published
2023
Full Text
View/download PDF

37. Supplementary Figures S1-S6 from Lipidomic Profiling of Clinical Prostate Cancer Reveals Targetable Alterations in Membrane Lipid Composition

Author

Butler, Lisa M., primary, Mah, Chui Yan, primary, Machiels, Jelle, primary, Vincent, Andrew D., primary, Irani, Swati, primary, Mutuku, Shadrack M., primary, Spotbeen, Xander, primary, Bagadi, Muralidhararao, primary, Waltregny, David, primary, Moldovan, Max, primary, Dehairs, Jonas, primary, Vanderhoydonc, Frank, primary, Bloch, Katarzyna, primary, Das, Rajdeep, primary, Stahl, Jurgen, primary, Kench, James G., primary, Gevaert, Thomas, primary, Derua, Rita, primary, Waelkens, Etienne, primary, Nassar, Zeyad D., primary, Selth, Luke A., primary, Trim, Paul J., primary, Snel, Marten F., primary, Lynn, David J., primary, Tilley, Wayne D., primary, Horvath, Lisa G., primary, Centenera, Margaret M., primary, and Swinnen, Johannes V., primary

Published
2023
Full Text
View/download PDF

38. Supplementary Tables S2-S6 from Lipidomic Profiling of Clinical Prostate Cancer Reveals Targetable Alterations in Membrane Lipid Composition

Author

Butler, Lisa M., primary, Mah, Chui Yan, primary, Machiels, Jelle, primary, Vincent, Andrew D., primary, Irani, Swati, primary, Mutuku, Shadrack M., primary, Spotbeen, Xander, primary, Bagadi, Muralidhararao, primary, Waltregny, David, primary, Moldovan, Max, primary, Dehairs, Jonas, primary, Vanderhoydonc, Frank, primary, Bloch, Katarzyna, primary, Das, Rajdeep, primary, Stahl, Jurgen, primary, Kench, James G., primary, Gevaert, Thomas, primary, Derua, Rita, primary, Waelkens, Etienne, primary, Nassar, Zeyad D., primary, Selth, Luke A., primary, Trim, Paul J., primary, Snel, Marten F., primary, Lynn, David J., primary, Tilley, Wayne D., primary, Horvath, Lisa G., primary, Centenera, Margaret M., primary, and Swinnen, Johannes V., primary

Published
2023
Full Text
View/download PDF

39. Tracer Lipidomics

Author

Dehairs, Jonas, primary, Koeken, Ine, additional, Quek, Lake‐Ee, additional, Hoy,, Andrew, additional, Ghesquière, Bart, additional, and Swinnen, Johannes V., additional

Published
2023
Full Text
View/download PDF

40. Additional file 1 of Pharmacological induction of membrane lipid poly-unsaturation sensitizes melanoma to ROS inducers and overcomes acquired resistance to targeted therapy

Author

Talebi, Ali, de Laat, Vincent, Spotbeen, Xander, Dehairs, Jonas, Rambow, Florian, Rogiers, Aljosja, Vanderhoydonc, Frank, Rizotto, Lara, Planque, Mélanie, Doglioni, Ginevra, Motamedi, Sahar, Nittner, David, Roskams, Tania, Agostinis, Patrizia, Bechter, Oliver, Boecxstaens, Veerle, Garmyn, Marjan, O’Farrell, Marie, Wagman, Alan, Kemble, George, Leucci, Eleonora, Fendt, Sarah-Maria, Marine, Jean-Christophe, and Swinnen, Johannes V.

Abstract

Additional file 1: Supplementary Figure S1. Lipogenic gene expression is associated with resistance to MAPKi therapy. Supplementary Figure S2. FASN and MAPK inhibition affect lipogenesis and lipid uptake. Supplementary Figure S3. Lipogenesis inhibition cooperates with MAPK inhibition to reduce cell proliferation. Supplementary Figure S4. ACACA and FASN knockdown cooperate with MAPK inhibition to reduce cell proliferation. Supplementary Figure S5. Lipogenesis inhibition cooperates with MAPK inhibition to reduce cell proliferation in BRAF wild-type cells. Supplementary Figure S6. MAPK inhibition response in Mel006 tumors is associated with membrane lipid polyunsaturation. Supplementary Figure S7. MAPK inhibition and FASN inhibition drive membrane polyunsaturation in D10 BMR cells. Supplementary Figure S8. MAPK inhibition and FASN inhibition increase membrane disorder in 451lu R and D10 BMR cells. Supplementary Figure S9. Phospholipidomics alterations following FASN and MAPK inhibition can be modulated by exogenous fatty acid supplementation in 451lu R. Supplementary Figure S10. Proliferation following FASN and MAPK inhibition can be modulated by exogenous fatty acid supplementation in D10 BMR cells. Supplementary Figure S11. Piperazine erastin and RSL3 sensitize D10 BMR cells to FASN and MAPK inhibition. Supplementary Figure S12. A host of ROS elevating compounds sensitize D10 BMR cells to FASN and MAPK inhibition. Supplementary Figure S13. Treatment combinations do not significantly alter mitochondrial membrane potential in 451lu R D10 BMR cells. Supplementary Figure S14. Exogenous fatty acid supplementation modulates the sensitivity of D10 BMR cells to FASN and MAPK inhibition in combination with ATO exposure. Supplementary Figure S15. Ferrostatin-1 but not ZVAD modulates the sensitivity of D10 BMR cells to FASN and MAPK inhibition in combination with ATO exposure. Supplementary Figure S16. The combination of FASN and MAPK inhibition with ATO treatment increases progression-free survival in Mel006 tumor bearing mice.

Published
2023
Full Text
View/download PDF

41. Additional file 3 of Pharmacological induction of membrane lipid poly-unsaturation sensitizes melanoma to ROS inducers and overcomes acquired resistance to targeted therapy

Author

Talebi, Ali, de Laat, Vincent, Spotbeen, Xander, Dehairs, Jonas, Rambow, Florian, Rogiers, Aljosja, Vanderhoydonc, Frank, Rizotto, Lara, Planque, Mélanie, Doglioni, Ginevra, Motamedi, Sahar, Nittner, David, Roskams, Tania, Agostinis, Patrizia, Bechter, Oliver, Boecxstaens, Veerle, Garmyn, Marjan, O’Farrell, Marie, Wagman, Alan, Kemble, George, Leucci, Eleonora, Fendt, Sarah-Maria, Marine, Jean-Christophe, and Swinnen, Johannes V.

Abstract

Additional file 3. Unedited Western Blots

Published
2023
Full Text
View/download PDF

42. Additional file 2 of Pharmacological induction of membrane lipid poly-unsaturation sensitizes melanoma to ROS inducers and overcomes acquired resistance to targeted therapy

Author

Talebi, Ali, de Laat, Vincent, Spotbeen, Xander, Dehairs, Jonas, Rambow, Florian, Rogiers, Aljosja, Vanderhoydonc, Frank, Rizotto, Lara, Planque, Mélanie, Doglioni, Ginevra, Motamedi, Sahar, Nittner, David, Roskams, Tania, Agostinis, Patrizia, Bechter, Oliver, Boecxstaens, Veerle, Garmyn, Marjan, O’Farrell, Marie, Wagman, Alan, Kemble, George, Leucci, Eleonora, Fendt, Sarah-Maria, Marine, Jean-Christophe, and Swinnen, Johannes V.

Abstract

Additional file 2. Mouse pathology report

Published
2023
Full Text
View/download PDF

43. Fatty acid elongation by ELOVL6 hampers remyelination by promoting inflammatory foam cell formation during demyelination.

Author

Corrales, Aida V. Garcia, Verberk, Sanne G. S., Haidar, Mansour, Grajchen, Elien, Dehairs, Jonas, Vanherle, Sam, Loix, Melanie, Weytjens, Tine, Gervois, Pascal, Takashi Matsuzaka, Lambrichts, Ivo, Swinnen, Johannes V., Bogie, Jeroen F. J., and Hendriks, Jerome J. A.

Subjects
FOAM cells, FATTY acids, MONOUNSATURATED fatty acids, UNSATURATED fatty acids, REMANUFACTURING, DEMYELINATION
Abstract

A hallmark of multiple sclerosis (MS) is the formation of multiple focal demyelinating lesions within the central nervous system (CNS). These lesions mainly consist of phagocytes that play a key role in lesion progression and remyelination, and therefore represent a promising therapeutic target in MS. We recently showed that unsaturated fatty acids produced by stearoyl-CoA desaturase-1 induce inflammatory foam cell formation during demyelination. These fatty acids are elongated by the "elongation of very long chain fatty acids" proteins (ELOVLs), generating a series of functionally distinct lipids. Here, we show that the expression and activity of ELOVLs are altered in myelin-induced foam cells. Especially ELOVL6, an enzyme responsible for converting saturated and monounsaturated C16 fatty acids into C18 species, was found to be up-regulated in myelin phagocytosing phagocytes in vitro and in MS lesions. Depletion of Elovl6 induced a repair-promoting phagocyte phenotype through activation of the S1P/PPAR? pathway. Elovl6-deficient foamy macrophages showed enhanced ABCA1-mediated lipid efflux, increased production of neurotrophic factors, and reduced expression of inflammatory mediators. Moreover, our data show that ELOVL6 hampers CNS repair, as Elovl6 deficiency prevented demyelination and boosted remyelination in organotypic brain slice cultures and the mouse cuprizone model. These findings indicate that targeting ELOVL6 activity may be an effective strategy to stimulate CNS repair in MS and other neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

45. Extracellular vesicle-associated cholesterol dictates the regenerative functions of macrophages in the brain

Author

Vanherle, Sam, primary, Guns, Jeroen, additional, Loix, Melanie, additional, Mingneau, Fleur, additional, Dierckx, Tess, additional, Vangansewinkel, Tim, additional, Wolfs, Esther, additional, Lins, Paula Pincela, additional, Bronckaers, Annelies, additional, Lambrichts, Ivo, additional, Dehairs, Jonas, additional, Swinnen, Johannes V., additional, Verberk, Sanne G.S., additional, Haidar, Mansour, additional, Hendriks, Jerome J.A., additional, and Bogie, Jeroen F.J., additional

Published
2022
Full Text
View/download PDF

47. Peroxisomal β-oxidation enzyme, DECR2, regulates lipid metabolism and promotes treatment resistance in advanced prostate cancer

Author

Mah, Chui Yan, primary, Nguyen, An Dieu Trang, additional, Niijima, Takuto, additional, Helm, Madison, additional, Dehairs, Jonas, additional, Ryan, Feargal J, additional, Ryan, Natalie, additional, Mills, Ian G, additional, Swinnen, Johannes V, additional, Lynn, David J, additional, Nassar, Zeyad D, additional, and Butler, Lisa M, additional

Published
2022
Full Text
View/download PDF

48. Disrupting peroxisomes alters lipid metabolism in melanoma and uncovers a novel therapeutic vulnerability in combination with MAPK-targeted therapies

Author

Huang, Fan, primary, Cai, Feiyang, additional, Dahabieh, Michael S., additional, Gunawardena, Kshemaka, additional, Talebi, Ali, additional, Dehairs, Jonas, additional, El-Turk, Farah, additional, Park, Jae Yeon, additional, Goncalves, Christophe, additional, Gagnon, Natascha, additional, Su, Jie, additional, Gaub, Perrine, additional, Joyal, Jean-Sébastien, additional, Mitchell, John J, additional, Swinnen, Johannes V, additional, Miller, Wilson H., additional, and del Rincón, Sonia V., additional

Published
2022
Full Text
View/download PDF

49. ACSM1 and ACSM3 regulate prostate cancer fatty acid metabolism to promote tumour growth and constrain ferroptosis

Author

Shrestha, Raj, primary, Nassar, Zeyad D., additional, Hanson, Adrienne R., additional, Iggo, Richard, additional, Townley, Scott L., additional, Dehairs, Jonas, additional, Mah, Chui Yan, additional, Helm, Madison, additional, Ghodsi, Mohammadreza, additional, Pickering, Marie, additional, Watt, Matthew J., additional, Quek, Lake-Ee, additional, Hoy, Andrew J., additional, Tilley, Wayne D., additional, Swinnen, Johannes V., additional, Butler, Lisa M., additional, and Selth, Luke A., additional

Published
2022
Full Text
View/download PDF

50. FTY720 decreases ceramides levels in the brain and prevents memory impairments in a mouse model of familial Alzheimer's disease expressing APOE4

Author

Crivelli, Simone M, Luo, Qian, Kruining, Daan van, Giovagnoni, Caterina, Mané-Damas, Marina, den Hoedt, Sandra, Berkes, Dusan, De Vries, Helga E, Mulder, Monique T, Walter, Jochen, Waelkens, Etienne, Derua, Rita, Swinnen, Johannes V, Dehairs, Jonas, Wijnands, Erwin P M, Bieberich, Erhard, Losen, Mario, Martinez-Martinez, Pilar, Molecular cell biology and Immunology, ACS - Microcirculation, Amsterdam Neuroscience - Neuroinfection & -inflammation, Amsterdam Neuroscience - Neurovascular Disorders, RS: MHeNs - R3 - Neuroscience, Psychiatrie & Neuropsychologie, Basic Neuroscience 3, Basic Neuroscience 1, and Internal Medicine

Subjects
FTY720, Sphingomyelin, APOE4, APOE3, Apolipoprotein E4, Anxiety, METABOLISM, Ceramides, S1P, 1-PHOSPHATE, INCREASE, MECHANISMS, Ceramide, Mice, SDG 3 - Good Health and Well-being, Alzheimer Disease, Memory, Animals, Humans, ACCUMULATION, Pharmacology, Memory Disorders, Sphingolipids, ROLES, SPHINGOSINE-1-PHOSPHATE, Fingolimod Hydrochloride, Brain, PATHWAYS, General Medicine, S1P Ceramide, 5xFAD, APOPTOSIS, AMYLOID PRECURSOR PROTEIN, Disease Models, Animal, lipids (amino acids, peptides, and proteins)
Abstract

The protection mediated by the bioactive sphingolipid sphingosine-1-phosphate (S1P) declines during Alzheimer's disease (AD) progression, especially in patients carrying the apolipoprotein E ε4 (APOE4) isoform. The drug FTY720 mimics S1P bioactivity, but its efficacy in treating AD is unclear. Two doses of FTY720 (0.1 mg / kg and 0.5 mg / kg daily) were given by oral gavage for 15 weeks to transgenic mouse models of familial AD carrying human apolipoprotein E (APOE) APOE3 (E3FAD) or APOE4 (E4FAD). After 12 weeks of treatment, animals were subjected to behavioral tests for memory, locomotion, and anxiety. Blood was withdrawn at different time points and brains were collected for sphingolipids analysis by mass spectrometry, gene expression by RT-PCR and Aβ quantification by ELISA. We discovered that low levels of S1P in the plasma is associated with a higher probability of failing the memory test and that FTY720 prevents memory impairments in E4FAD. The beneficial effect of FTY720 was induced by a shift of the sphingolipid metabolism in the brain towards a lower production of toxic metabolites, like ceramide d18:1/16:0 and d18:1/22:0, and reduction of amyloid-β burden and inflammation. In conclusion, we provide further evidence of the druggability of the sphingolipid system in AD. ispartof: BIOMEDICINE & PHARMACOTHERAPY vol:152 ispartof: location:France status: published

Published
2022

Catalog

Books, media, physical & digital resources
See catalog results