Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond
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TLDR
The ways in which S1P might be therapeutically targeted are discussed — for example, via the development of chemical inhibitors that target the generation, transport and degradation of S 1P and via thedevelopment of specific S1p receptor agonists.Abstract:
The bioactive lipid sphingosine-1-phosphate (S1P) is involved in multiple cellular signalling systems and has a pivotal role in the control of immune cell trafficking. As such, S1P has been implicated in disorders such as cancer and inflammatory diseases. This Review discusses the ways in which S1P might be therapeutically targeted — for example, via the development of chemical inhibitors that target the generation, transport and degradation of S1P and via the development of specific S1P receptor agonists. We also highlight recent conflicting results observed in preclinical studies targeting S1P and discuss ongoing clinical trials in this field.read more
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Inhibitors of Ceramidases.
Essa M. Saied,Christoph Arenz +1 more
TL;DR: The development of ceramide analogues as first-generation ceramidase inhibitors together with data on their activity in cells and disease models are summarized and the recent developments that have led to highly potent second-generation ceramicamidases inhibitors that act at nanomolar concentrations are described.
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Involvement of CETP (Cholesteryl Ester Transfer Protein) in the Shift of Sphingosine-1-Phosphate Among Lipoproteins and in the Modulation of its Functions
TL;DR: CETP modulates the distribution of S1P among lipoproteins, which affects the bioactivities of S2P and apolipoprotein M (apoM), a carrier of S 1P, in the total plasma.
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Current Understanding of the Pathways Involved in Adult Stem and Progenitor Cell Migration for Tissue Homeostasis and Repair.
TL;DR: An overview of studies addressing the physiological significance and diverse modes of stem and progenitor cell trafficking in adult mammalian organs is provided, the major microenvironmental cues regulating cell migration are discussed, and the implementation of live imaging approaches for the exploration of stem cell movement in tissues are described.
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Biological Effects of Naturally Occurring Sphingolipids, Uncommon Variants, and Their Analogs
Mitchell K.P. Lai,Wee Siong Chew,Federico Torta,Angad Rao,Greg L. Harris,Jerold Chun,Deron R. Herr,Deron R. Herr +7 more
TL;DR: An overview of SP metabolism and signaling, their perturbations in neurological diseases, as well as potential impacts of modulating this system in the brain are provided.
Journal ArticleDOI
Sphingosine-1-phosphate (S1P) induces potent anti-inflammatory effects in vitro and in vivo by S1P receptor 4-mediated suppression of 5-lipoxygenase activity
Jasmin Fettel,Benjamin Kühn,Nathalie Guillen,Duran Sürün,Marcus Peters,Rebekka Bauer,Carlo Angioni,Gerd Geisslinger,Frank Schnütgen,Dagmar Meyer zu Heringdorf,Oliver Werz,Patrick Meybohm,Kai Zacharowski,Dieter Steinhilber,Jessica Roos,Thorsten J. Maier +15 more
TL;DR: It is reported for the first time that S1P potently suppresses LT biosynthesis in Ca2+‐ionophore–stimulated intact human neutrophils and targeting the 5‐LO pathway is an important mechanism to explain S 1P‐mediated pathophysiologic effects.
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