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
Pharmacology & Pharmacy
Andrea C. Diaz C. Diaz, Kyle Malone, Jennifer A. Shearer, Anne C. Moore, Christian Waeber
Summary: This study used a rigorous study design to evaluate the translational potential of fingolimod in the treatment of stroke. The results show that the effects of fingolimod vary in different mouse models and may depend on the inflammatory status of the animals.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Sekhar Surapaneni, Usha Yerramilli, April Bai, Deepak Dalvie, Jennifer Brooks, Xiaomin Wang, Julie Selkirk, Yingzhuo Grace Yan, Peijin Zhang, Richard Hargreaves, Gondi Kumar, Maria Palmisano, Jonathan Q. Tran
Summary: Absorption, metabolism, and excretion of ozanimod in humans were characterized, and the enzymes involved in complex metabolism were elucidated. Disproportionate metabolites were identified, and the activity of these metabolites was determined.
DRUG METABOLISM AND DISPOSITION
(2021)
Review
Pharmacology & Pharmacy
Gerhild van Echten-Deckert
Summary: Lipids are essential components of the CNS, and sphingolipids, a type of lipid, are highly concentrated in the brain. Sphingosine 1-phosphate (S1P), derived from membrane sphingolipids, has complex effects on the brain, which can be both beneficial and detrimental. However, the role of S1P in brain development and various brain pathologies is still controversial.
PHARMACOLOGY & THERAPEUTICS
(2023)
Review
Clinical Neurology
Shitiz Sriwastava, Durgesh Chaudhary, Samiksha Srivastava, Katherine Beard, Xue Bai, Sijin Wen, Syed Hassan Khalid, Robert P. Lisak
Summary: The incidence of PML in MS patients treated with S1PR modulators like fingolimod appears to be extremely low. Risk of PML increases with longer duration of treatment with S1PR modulators, and older age at the time of PML diagnosis is associated with worse prognosis.
JOURNAL OF NEUROLOGY
(2022)
Review
Immunology
Hans-Peter Hartung, Bruce A. C. Cree, Michael Barnett, Sven G. Meuth, Amit Bar-Or, Lawrence Steinman
Summary: Disease-modifying therapies for relapsing multiple sclerosis reduce relapse rates by suppressing peripheral immune cells but have limited efficacy in progressive forms of the disease. Cladribine and sphingosine 1-phosphate receptor modulators could have beneficial direct central nervous system properties.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Pharmacology & Pharmacy
Jerold Chun, Gavin Giovannoni, Samuel F. Hunter
Summary: Lysophospholipids, particularly sphingosine 1-phosphate (S1P), act through G protein-coupled receptors (GPCRs) and have complex effects on physiological and pathophysiological events. S1PR modulators, including fingolimod, siponimod, and ozanimod, have been approved for multiple sclerosis (MS) treatment, with others like ponesimod and etrasimod in clinical development. These modulators show subtype specificity for S1PRs, influencing downstream effects, and can act as both agonists and functional antagonists.
Article
Pharmacology & Pharmacy
Carlo Gesualdo, Cornel Balta, Chiara Bianca Maria Platania, Maria Consiglia Trotta, Hildegard Herman, Sami Gharbia, Marcel Rosu, Francesco Petrillo, Salvatore Giunta, Alberto Della Corte, Paolo Grieco, Rosa Bellavita, Francesca Simonelli, Michele D'Amico, Anca Hermenean, Settimio Rossi, Claudio Bucolo
Summary: The anti-angiogenic activity of fingolimod in diabetic retinopathy mouse models may be mediated not only through S1P1R but also through melanocortin receptors MC1R and MC5R.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Oncology
Yuko Tanaka, Seiichi Okabe, Kazuma Ohyashiki, Akihiko Gotoh
Summary: This study found that S1P activation is associated with proliferation and survival of MM cells, and S1P attenuates the effect of proteasome inhibitors (PI). Anti-S1P agents can inhibit MM cell proliferation, promote apoptosis, and reduce the impact of S1P on cell migration. These findings highlight the potential therapeutic value of anti-S1P agents in MM treatment.
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.
Review
Cell Biology
Simela Chatzikonstantinou, Vasiliki Poulidou, Marianthi Arnaoutoglou, Dimitrios Kazis, Ioannis Heliopoulos, Nikolaos Grigoriadis, Marina Boziki
Summary: Sphingosine 1-phosphate (S1P) is a crucial signaling molecule with diverse biological functions that are mediated through its receptors, playing a significant role in cell proliferation, immune responses, and gut-brain axis regulation. The modulation of S1PR has promising therapeutic potential in immune-mediated diseases like multiple sclerosis by affecting immune cells, gut barrier, and the central nervous system.
Article
Multidisciplinary Sciences
Hongwen Chen, Kevin Chen, Weijiao Huang, Louis M. Staudt, Jason G. Cyster, Xiaochun Li
Summary: This article presents the cryo-electron microscopy structure of S1P-bound S1PR2 coupled to the heterotrimeric G(13), revealing key roles of residues in S1PR2-G(alpha 13) complex assembly. The structure illuminates the mechanism of receptor disruption by disease-associated mutations.
Article
Medicine, General & Internal
Gianmarco Abbadessa, Elisabetta Maida, Giuseppina Miele, Floriana Bile, Luigi Lavorgna, Simona Bonavita
Summary: This study reports three SPMS patients experiencing disease reactivation in the first three months after switching from fingolimod to siponimod, possibly due to the differential effects of Siponimod on S1P3 receptors.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Gastroenterology & Hepatology
Jie Wang, Idan Goren, Bo Yang, Sinan Lin, Jiannan Li, Michael Elias, Claudio Fiocchi, Florian Rieder
Summary: S1P receptor modulators are a novel, promising, and safe strategy for the treatment of IBD, with several potential candidates showing positive results in clinical trials.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Cell Biology
Alessandra Roggeri, Guendalina Olivero, Cesare Usai, Tim Vanmierlo, Anna Pittaluga
Summary: This study provides evidence of the existence and distribution of inhibitory S1P1R and facilitatory S1P3R in cortical nerve endings of healthy mice. It also shows that the activity of these receptors is amplified in mice with experimental autoimmune encephalomyelitis (EAE) but can be recovered after chronic FTY720 treatment.
Article
Immunology
Jack P. Antel, Yun Hsuan Lin, Qiao-Ling Cui, Florian Pernin, Timothy E. Kennedy, Samuel K. Ludwin, Luke M. Healy
JOURNAL OF NEUROIMMUNOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Michael A. Wheeler, Merja Jaronen, Ruxandra Covacu, Stephanie E. J. Zandee, Giulia Scalisi, Veit Rothhammer, Emily C. Tjon, Chun-Cheih Chao, Jessica E. Kenison, Manon Blain, Vijayaraghava T. S. Rao, Patrick Hewson, Andreia Barroso, Cristina Gutierrez-Vazquez, Alexandre Prat, Jack P. Antel, Russ Hauser, Francisco J. Quintana
Article
Neurosciences
Brandon Stopnicki, Manon Blain, Qiao-Ling Cui, Timothy E. Kennedy, Jack P. Antel, Luke M. Healy, Peter J. Darlington
Editorial Material
Clinical Neurology
Alan J. Thompson, Jack Antel, William (Bill) Carroll, Jeroen Geurts
MULTIPLE SCLEROSIS JOURNAL
(2019)
Correction
Immunology
R. Li, A. Rezk, M. Ghadiri, F. Luessi, F. Zipp, H. Li, P. S. Giacomini, J. Antel, A. Bar-Or
JOURNAL OF IMMUNOLOGY
(2019)
Article
Clinical Neurology
Caroline Esmonde-White, Moein Yaqubi, Philippe A. Bilodeau, Qiao Ling Cui, Florian Pernin, Catherine Larochelle, Mahtab Ghadiri, Yu Kang T. Xu, Timothy E. Kennedy, Jeffery Hall, Luke M. Healy, Jack P. Antel
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2019)
Article
Neurosciences
Maisa C. Takenaka, Galina Gabriely, Veit Rothhammer, Ivan D. Mascanfroni, Michael A. Wheeler, Chun-Cheih Chao, Cristina Gutierrez-Vazquez, Jessica Kenison, Emily C. Tjon, Andreia Barroso, Tyler Vandeventer, Kalil Alves de Lima, Sonja Rothweiler, Lior Mayo, Soufiene Ghannam, Stephanie Zandee, Luke Healy, David Sherr, Mauricio F. Farez, Alexandre Pratt, Jack Antel, David A. Reardon, Hailei Zhang, Simon C. Robson, Gad Getz, Howard L. Weiner, Francisco J. Quintana
NATURE NEUROSCIENCE
(2019)
Article
Nutrition & Dietetics
Lars Libuda, Bjoern-Hergen Laabs, Christine Ludwig, Judith Buehlmeier, Jochen Antel, Anke Hinney, Roaa Naaresh, Manuel Foecker, Johannes Hebebrand, Inke R. Koenig, Triinu Peters
Article
Medicine, Research & Experimental
Laura A. Vella, Marcus Buggert, Sasikanth Manne, Ramin S. Herati, Ismail Sayin, Leticia Kuri-Cervantes, Irene Bukh Brody, Kaitlin C. O'Boyle, Hagop Kaprielian, Josephine R. Giles, Son Nguyen, Alexander Muselman, Jack P. Antel, Amit Bar-Or, Matthew E. Johnson, David H. Canaday, Ali Naji, Vitaly V. Ganusov, Terri M. Laufer, Andrew D. Wells, Yoav Dori, Maxim G. Itkin, Michael R. Betts, E. John Wherry
JOURNAL OF CLINICAL INVESTIGATION
(2019)
Article
Public, Environmental & Occupational Health
Bochao D. Lin, Anne Alkema, Triinu Peters, Janneke Zinkstok, Lars Libuda, Johannes Hebebrand, Jochen Antel, Anke Hinney, Wiepke Cahn, Roger Adan, Jurjen J. Luykx
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
(2019)
Review
Neurosciences
Luke M. Healy, Moein Yaqubi, Samuel Ludwin, Jack P. Antel
Article
Clinical Neurology
Vijayaraghava T. S. Rao, Shih-Chieh Fuh, Jason R. Karamchandani, John M. J. Woulfe, David G. Munoz, Benjamin Ellezam, Manon Blain, Ming-Kai Ho, Barry J. Bedell, Jack P. Antel, Samuel K. Ludwin
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2019)
Article
Immunology
Jenna L. Pappalardo, Le Zhang, Maggie K. Pecsok, Kelly Perlman, Chrysoula Zografou, Khadir Raddassi, Ahmad Abulaban, Smita Krishnaswamy, Jack Antel, David van Dijk, David A. Hafler
SCIENCE IMMUNOLOGY
(2020)
Review
Biology
Irene Molina-Gonzalez, Veronique E. Miron, Jack P. Antel
Summary: This Perspective discusses the contribution of oligodendrocyte injury to neurological disease and the potential for therapeutic targeting. Targeting mature oligodendrocyte health is proposed as a promising therapeutic strategy to support central nervous system function.
COMMUNICATIONS BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Evan Rizzel Gran, Franck Bertorelle, Hussein Fakhouri, Rodolphe Antoine, Martina Peric Bakulic, Zeljka Sanader Marsic, Vlasta Bonacic-Koutecky, Manon Blain, Jack Antel, Dusica Maysinger
Summary: The study reveals that ultra-small gold nanoclusters are not inert in human primary astrocytes and play a critical role in modulation of organellar and redox-responsive transcription factor homeostasis. Size-dependent effects were most remarkable with smaller and larger AuNCs, potentially related to their accessibility to biological targets.