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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Sphingosine-1-Phosphate (S1P) Impacts Presynaptic Functions by Regulating Synapsin I Localization in the Presynaptic Compartment
Loredana Riganti,Flavia Antonucci,Martina Gabrielli,Ilaria Prada,Paola Giussani,Paola Viani,Flavia Valtorta,Elisabetta Menna,Michela Matteoli,Claudia Verderio +9 more
TL;DR: Evidence is provided that S1P can be produced at mature axon terminals as well as at immature growth cones in response to microglia-derived signals, which may be important to stabilize nascent synapses and to restore or potentiate transmission.
Journal ArticleDOI
Breast cancer sphingosine-1-phosphate is associated with phospho-sphingosine kinase 1 and lymphatic metastasis
Junko Tsuchida,Masayuki Nagahashi,Masato Nakajima,Kazuki Moro,Kumiko Tatsuda,Rajesh Ramanathan,Kazuaki Takabe,Toshifumi Wakai +7 more
TL;DR: This is the first study to demonstrate that high expression of pSphK1 is associated with higher levels of S1P, which in turn isassociated with lymphatic metastasis in breast cancer.
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Protein phosphatase 2A as a therapeutic target in inflammation and neurodegeneration
Andrew R. Clark,Michael Ohlmeyer +1 more
TL;DR: The concept that PP2A also constrains inflammatory responses through its inhibitory effects on various signalling pathways is explored, suggesting that PADs may be effective in the treatment of inflammation-mediated pathologies.
Journal ArticleDOI
Quantification of sphingosine 1-phosphate by validated LC-MS/MS method revealing strong correlation with apolipoprotein M in plasma but not in serum due to platelet activation during blood coagulation
Cecilia Frej,Anders S Andersson,Benny Larsson,Li Jun Guo,Eva Norström,Kaisa E. Happonen,Björn Dahlbäck +6 more
TL;DR: It is found that the methanol precipitation used to extract S1P co-extracted apoM and several other HDL-proteins from plasma, thus increasing the S 1P concentration to double in serum as compared to that in plasma.
Journal ArticleDOI
Macrophage-Bacteria Interactions-A Lipid-Centric Relationship.
TL;DR: The emerging roles of lipids in the complex host–pathogen relationship are reviewed and recent methodologies employed to probe these versatile metabolites during the infection process are discussed.
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