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Your search keyword '"Alnouri, Mohamad Wessam"' showing total 14 results
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14 results on '"Alnouri, Mohamad Wessam"'

3. Identification of a Chemical Probe for BLT2 Activation by Scaffold Hopping.

Author

Hernandez-Olmos, Victor, Heering, Jan, Ildefeld, Niklas, Ehrler, Johanna H. M., Kaps, Alexander, Rajkumar, Rinusha, Marinescu, Beatrice, Kaiser, Astrid, Macinkovic, Igor, Elewa, Mohammed A. F., Alnouri, Mohamad Wessam, Elson, Lewis, Schubert-Zsilavecz, Manfred, Kallenborn-Gerhardt, Wiebke, Schmidtko, Achim, Müller, Susanne, Offermanns, Stefan, Steinhilber, Dieter, Weigert, Andreas, and Proschak, Ewgenij

Published
2025
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5. SPMs exert anti-inflammatory and pro-resolving effects through positive allosteric modulation of the prostaglandin EP4 receptor.

Author

Alnouri, Mohamad Wessam, Roquid, Kenneth Anthony, Bonnavion, Rémy, Cho, Haaglim, Heering, Jan, Kwon, Jeonghyeon, Jäger, Yannick, Wang, ShengPeng, Günther, Stefan, Wettschureck, Nina, Geisslinger, Gerd, Gurke, Robert, Müller, Christa E., Proschak, Ewgenij, and Offermanns, Stefan

Subjects
*ALLOSTERIC regulation, *OMEGA-3 fatty acids, *PROSTAGLANDIN receptors, *ANTI-inflammatory agents, *BINDING sites
Abstract

Inflammation is a protective response to pathogens and injury. To be effective it needs to be resolved by endogenous mechanisms in order to avoid prolonged and excessive inflammation, which can become chronic. Specialized pro-resolving mediators (SPMs) are a group of lipids derived from omega-3 fatty acids, which can induce the resolution of inflammation. How SPMs exert their anti-inflammatory and pro-resolving effects is, however, not clear. Here, we show that SPMs such as protectins, maresins, and D-series resolvins function as biased positive allosteric modulators (PAM) of the prostaglandin E2 (PGE2) receptor EP4 through an intracellular binding site. They increase PGE2-induced Gs-mediated formation of cAMP and thereby promote anti-inflammatory signaling of EP4. In addition, SPMs endow the endogenous EP4 receptor on macrophages with the ability to couple to Gi-type G-proteins, which converts the EP4 receptor on macrophages from an anti-phagocytotic receptor to one increasing phagocytosis, a central mechanism of the pro-resolving activity of synthetic SPMs. In the absence of the EP4 receptor, SPMs lose their anti-inflammatory and pro-resolving activity in vitro and in vivo. Our findings reveal an unusual mechanism of allosteric receptor modulation by lipids and provide a mechanism by which synthetic SPMs exert pro-resolving and anti-inflammatory effects, which may facilitate approaches to treat inflammation. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Development of a Potent and Selective G2A (GPR132) Agonist.

Author

Hernandez-Olmos, Victor, Heering, Jan, Marinescu, Beatrice, Schermeng, Tina, Ivanov, Vladimir V., Moroz, Yurii S., Nevermann, Sheila, Mathes, Marius, Ehrler, Johanna H. M., Alnouri, Mohamad Wessam, Wolf, Markus, Haydo, Alicia S., Schmachtel, Tessa, Zaliani, Andrea, Höfner, Georg, Kaiser, Astrid, Schubert-Zsilavecz, Manfred, Beck-Sickinger, Annette G., Offermanns, Stefan, and Gribbon, Philipp

Published
2024
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8. A succinate/SUCNR1-brush cell defense program in the tracheal epithelium

Author

Perniss, Alexander, primary, Boonen, Brett, additional, Tonack, Sarah, additional, Thiel, Moritz, additional, Poharkar, Krupali, additional, Alnouri, Mohamad Wessam, additional, Keshavarz, Maryam, additional, Papadakis, Tamara, additional, Wiegand, Silke, additional, Pfeil, Uwe, additional, Richter, Katrin, additional, Althaus, Mike, additional, Oberwinkler, Johannes, additional, Schütz, Burkhard, additional, Boehm, Ulrich, additional, Offermanns, Stefan, additional, Leinders-Zufall, Trese, additional, Zufall, Frank, additional, and Kummer, Wolfgang, additional

Published
2023
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9. A succinate/SUCNR1-brush cell defense program in the tracheal epithelium

Author

Perniss, Alexander, Boonen, Brett, Tonack, Sarah, Thiel, Moritz, Poharkar, Krupali, Alnouri, Mohamad Wessam, Keshavarz, Maryam, Papadakis, Tamara, Wiegand, Silke, Pfeil, Uwe, Richter, Katrin, Althaus, Mike, Oberwinkler, Johannes, Schütz, Burkhard, Boehm, Ulrich, Offermanns, Stefan, Leinders-Zufall, Trese, Zufall, Frank, Kummer, Wolfgang, Perniss, Alexander, Boonen, Brett, Tonack, Sarah, Thiel, Moritz, Poharkar, Krupali, Alnouri, Mohamad Wessam, Keshavarz, Maryam, Papadakis, Tamara, Wiegand, Silke, Pfeil, Uwe, Richter, Katrin, Althaus, Mike, Oberwinkler, Johannes, Schütz, Burkhard, Boehm, Ulrich, Offermanns, Stefan, Leinders-Zufall, Trese, Zufall, Frank, and Kummer, Wolfgang

Published
2023

12. The FKBP51 Inhibitor SAFit2 Restores the Pain-Relieving C16 Dihydroceramide after Nerve Injury

Author

Wedel, Saskia, Hahnefeld, Lisa, Alnouri, Mohamad Wessam, Offermanns, Stefan, Hausch, Felix, Geisslinger, Gerd, Sisignano, Marco, Wedel, Saskia, Hahnefeld, Lisa, Alnouri, Mohamad Wessam, Offermanns, Stefan, Hausch, Felix, Geisslinger, Gerd, and Sisignano, Marco

Abstract

Neuropathic pain is a pathological pain state with a broad symptom scope that affects patients after nerve injuries, but it can also arise after infections or exposure to toxic substances. Current treatment possibilities are still limited because of the low efficacy and severe adverse effects of available therapeutics, highlighting an emerging need for novel analgesics and for a detailed understanding of the pathophysiological alterations in the onset and maintenance of neuropathic pain. Here, we show that the novel and highly specific FKBP51 inhibitor SAFit2 restores lipid signaling and metabolism in nervous tissue after nerve injury. More specifically, we identify that SAFit2 restores the levels of the C16 dihydroceramide, which significantly reduces the sensitization of the pain-mediating TRPV1 channel and subsequently the secretion of the pro-inflammatory neuropeptide CGRP in primary sensory neurons. Furthermore, we show that the C16 dihydroceramide is capable of reducing acute thermal hypersensitivity in a capsaicin mouse model. In conclusion, we report for the first time the C16 dihydroceramide as a novel and crucial lipid mediator in the context of neuropathic pain as it has analgesic properties, contributing to the pain-relieving properties of SAFit2.

Published
2022

13. Formation, Signaling and Occurrence of Specialized Pro-Resolving Lipid Mediators—What is the Evidence so far?

Author

Schebb, Nils Helge, primary, Kühn, Hartmut, additional, Kahnt, Astrid S., additional, Rund, Katharina M., additional, O’Donnell, Valerie B., additional, Flamand, Nicolas, additional, Peters-Golden, Marc, additional, Jakobsson, Per-Johan, additional, Weylandt, Karsten H., additional, Rohwer, Nadine, additional, Murphy, Robert C., additional, Geisslinger, Gerd, additional, FitzGerald, Garret A., additional, Hanson, Julien, additional, Dahlgren, Claes, additional, Alnouri, Mohamad Wessam, additional, Offermanns, Stefan, additional, and Steinhilber, Dieter, additional

Published
2022
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