Article
Biochemistry & Molecular Biology
Zafrul Hasan, Toan Q. Nguyen, Brenda Wan Shing Lam, Jovi Hui Xin Wong, Caleb Cheng Yi Wong, Clarissa Kai Hui Tan, Jiabo Yu, Chung Hwee Thiam, Yongliang Zhang, Veronique Angeli, Long N. Nguyen
Summary: The protein Spns2 is involved in regulating lymphocyte movement and has been shown to have potential as a drug target in autoimmune diseases. This study examined mice with a genetic deletion of Spns2 and found that it affected lymphocyte levels, S1P secretion, and lymph node vasculature. Additionally, these mice were resistant to multiple sclerosis, suggesting that targeting Spns2 could be a promising therapeutic approach for neuroinflammation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Chemistry, Medicinal
Ariel L. Burgio, Christopher W. Shrader, Yugesh Kharel, Tao Huang, Joseph M. Salamoun, Kevin R. Lynch, Webster L. Santos
Summary: The S1P1 receptor is targeted by four drugs in the treatment of multiple sclerosis and ulcerative colitis. Targeting Spns2, an S1P exporter, upstream of S1P receptor engagement may provide an alternative strategy to mimic the efficacy of S1P receptor modulators without cardiac toxicity.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
Emanuela Colombo, Cinthia Farina
Summary: Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that binds to specific G protein-coupled receptors expressed in various organs. Targeting S1P receptors with modulators has shown potential in treating neurological, autoimmune, and inflammatory disorders. These modulators induce lymphopenia and may have immunological effects beyond lymphocyte trafficking inhibition. They can also cross the blood-brain barrier and target CNS resident cells expressing S1P receptors. Understanding the role of S1P signaling in neuroimmunology has important implications for therapeutic approaches in other disease areas.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Cell Biology
Martyna Okuniewska, Victoria Fang, Audrey Baeyens, Varsha Raghavan, June-Yong Lee, Dan R. Littman, Susan R. Schwab
Summary: The text discusses the role of S1P receptor 1 in T cell exit from lymph nodes and vascular permeability regulation. It also highlights the therapeutic potential of targeting S1PR1 for autoimmune diseases. The importance of SPNS2 in supplying lymph S1P and supporting T cell exit is emphasized, but further research is needed to determine its necessity during immune responses.
Article
Pharmacology & Pharmacy
Julie V. Selkirk, Yingzhuo Grace Yan, Nathan Ching, Kate Paget, Richard Hargreaves
Summary: Ozanimod and its metabolites bind to and activate sphingosine 1-phosphate receptors 1 and 5, displaying similar pharmacologic profiles. This contributes to their clinical efficacy in treating patients with relapsing multiple sclerosis or moderately to severely active ulcerative colitis.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Cell Biology
Fei Li, Yifan Zhang, Zhoujun Lin, Lizhong Yan, Qiao Liu, Yin Li, Xiaolin Pei, Ya Feng, Xiao Han, Juan Yang, Fangxu Zheng, Tianjiao Li, Yupeng Zhang, Zhenkun Fu, Di Shao, Jane Yu, Chenggang Li
Summary: This study identified rapamycin-insensitive sphingosine metabolic signatures in LAM cells and demonstrated that therapeutic targeting of aberrant SPHK1/S1P/S1PR3 signaling may have potent therapeutic benefit for patients with TSC/LAM or other hyperactive mTOR neoplasms with autophagy inhibition.
CELL DEATH & DISEASE
(2022)
Article
Neurosciences
Huitong Song, Holly P. McEwen, Thomas Duncan, Jun Yup Lee, Jonathan D. Teo, Anthony S. Don
Summary: SphK2 deficiency leads to decreased remyelination and maintenance of myelin with aging, possibly due to elevated levels of cytotoxic sphingosine and ceramide.
Article
Cell & Tissue Engineering
Chelsea A. Saito-Reis, Victoria D. Balise, Erica M. Pascetti, Magdalena Jiminez, Jennifer M. Gillette
Summary: The study identifies CD82 as a novel regulator of HSPC mobilization, showing enhanced HSPC mobilization in CD82KO mice and an effect on S1PR(1) surface regulation. Combining AMD3100 and anti-CD82 treatments can enhance the mobilization of mouse HSPCs and human CD34+ cells.
Article
Neurosciences
Junhua Xiao
Summary: Sphingosine 1-phosphate lyase (SPL) is a key enzyme in sphingolipid metabolism and has potential as a therapeutic target. Its role in the developing nervous system is unclear, but in adults, loss of SPL activity appears to be neuroprotective in acquired neurological disorders. Further research is needed to understand the precise function of SPL in the nervous system and develop S1P-based therapies for neuroprotection.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Cell Biology
Yaeni Kim, Ji Hee Lim, Eun Nim Kim, Yu Ah Hong, Hun-Jun Park, Sungjin Chung, Bum Soon Choi, Yong-Soo Kim, Ji Yong Park, Hye Won Kim, Cheol Whee Park
Summary: This study found that AdipoRon improved cardiac lipid metabolism, hypertrophy, and functional parameters by increasing AdipoR expression, acid ceramidase activity, and activating AMPK-PPAR alpha/PGC-1 alpha and related downstream pathways.
CELL DEATH & DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Janik Riese, Alina Gromann, Felix Luehrs, Annabel Kleinwort, Tobias Schulze
Summary: This study found that under inflammatory conditions, S1P-mediated signaling controls the migration of peritoneal B cells, and deficiency of S1P(4) affects the trafficking of activated peritoneal B cells to secondary lymphoid organs and their positioning.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Peripheral Vascular Disease
Amra Jujic, Frank Matthes, Lotte Vanherle, Henning Petzka, Marju Orho-Melander, Peter M. Nilsson, Martin Magnusson, Anja Meissner
Summary: The study found an association between plasma S1P and elevated systolic blood pressure, validated in both a mouse model and in humans. Further proteomic analysis revealed multiple S1P associations, some of which were sex-specific. In vitro and in vivo validation showed increased expression of vascular dysfunction and inflammation markers in response to S1P.
Article
Pharmacology & Pharmacy
Bradley S. Fleenor, Nicholas A. Carlini, An Ouyang, Matthew P. Harber
Summary: Cardiovascular diseases are the leading cause of death in modern societies, and arterial stiffening plays a crucial role in the development of these diseases. Perivascular adipose tissue, a relatively understudied fat depot, has direct and profound effects on arterial stiffening. Identifying it as a therapeutic target to lower arterial stiffness and reduce cardiovascular disease risk has significant clinical implications.
PHARMACOLOGICAL RESEARCH
(2022)
Review
Medicine, General & Internal
Ralf A. Claus, Markus H. Graeler
Summary: Sphingolipids are a highly diverse group of lipids with mass spectrometry being a valuable tool for their qualitative and quantitative identification, especially in biomedical applications. Therefore, considering the entire experimental strategy is crucial, from sample collection and preparation to data analysis and interpretation. Expert opinions suggest that mass spectrometry plays a key role in investigating cellular and compartment-specific stress responses, with the integration of multiple datasets being crucial for understanding human health and disease response.
FRONTIERS IN MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Elisabetta Meacci, Federica Pierucci, Mercedes Garcia-Gil
Summary: SARS-CoV-2 virus infection can cause COVID-19, which has a wide range of manifestations and can persist for months. The musculoskeletal system is considered important in both COVID-19 patients and those recovering from the infection. Musculoskeletal manifestations include muscle loss, weakness, fatigue or myalgia, and injury. The role of sphingosine 1-phosphate signaling in predicting and treating musculoskeletal manifestations of virus infection in COVID-19 is highlighted.