scholarly journals SARS-CoV-2 Infection: A Role for S1P/S1P Receptor Signaling in the Nervous System?

2020 ◽  
Vol 21 (18) ◽  
pp. 6773 ◽  
Author(s):  
Elisabetta Meacci ◽  
Mercedes Garcia-Gil ◽  
Federica Pierucci
Keyword(s):  
Nervous System ◽  
Clinical Manifestations ◽  
Virus Propagation ◽  
Angiotensin Converting Enzyme 2 ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor ◽  
Virus Interaction ◽  
Cell Niche ◽  
Pleiotropic Properties

The recent coronavirus disease (COVID-19) is still spreading worldwide. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus responsible for COVID-19, binds to its receptor angiotensin-converting enzyme 2 (ACE2), and replicates within the cells of the nasal cavity, then spreads along the airway tracts, causing mild clinical manifestations, and, in a majority of patients, a persisting loss of smell. In some individuals, SARS-CoV-2 reaches and infects several organs, including the lung, leading to severe pulmonary disease. SARS-CoV-2 induces neurological symptoms, likely contributing to morbidity and mortality through unknown mechanisms. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid with pleiotropic properties and functions in many tissues, including the nervous system. S1P regulates neurogenesis and inflammation and it is implicated in multiple sclerosis (MS). Notably, Fingolimod (FTY720), a modulator of S1P receptors, has been approved for the treatment of MS and is being tested for COVID-19. Here, we discuss the putative role of S1P on viral infection and in the modulation of inflammation and survival in the stem cell niche of the olfactory epithelium. This could help to design therapeutic strategies based on S1P-mediated signaling to limit or overcome the host–virus interaction, virus propagation and the pathogenesis and complications involving the nervous system.

scholarly journals Nervous system injury in alcoholic disease

2019 ◽  
Vol 11 (2S) ◽  
pp. 83-88
Author(s):  
O. E. Zinovyeva ◽  
N. V. Vashchenko ◽  
O. E. Mozgovaya ◽  
T. A. Yanakaeva ◽  
A. Yu. Emelyanova
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Alcohol Intoxication ◽  
Clinical Manifestations ◽  
Symptomatic Treatment ◽  
Chronic Alcohol ◽  
Neurological Manifestations ◽  
Chronic Alcohol Intoxication ◽  
Alcoholic Disease

The paper considers various variants of nervous system injury in alcoholic disease. It discusses the epidemiology, pathogenesis, diagnosis, and clinical manifestations of central and peripheral nervous system lesions in the presence of acute and chronic alcohol intoxication. Attention is paid to the issues of etiotropic, pathogenetic, and symptomatic treatment for neurological manifestations of alcoholic disease and to the role of neurotropic B vitamins in the treatment of alcohol-induced deficiency and non-deficiency states.

scholarly journals The role of membrane-destabilizing processes in the pathogenesis and clinical manifestations of perinatal encephalopathy in children

2001 ◽  
Vol 82 (2) ◽  
pp. 137-138
Author(s):  
E. V. Levitina ◽  
G. A. Ivanichev ◽  
M. M. Minnibaev
Keyword(s):  
Nervous System ◽  
Early Diagnosis ◽  
Clinical Manifestations ◽  
Perinatal Period ◽  
Diagnosis And Treatment ◽  
Definition Of ◽  
Methods Of Treatment ◽  
All Diseases ◽  
Made In

2/3 of all diseases of the nervous system in children begin to develop in the perinatal period. In recent decades, great strides have been made in perinatal neurology in the development of criteria for early diagnosis and treatment of diseases. Further study of the biochemical foundations of perinatal lesions of the nervous system with the definition of objective markers of the severity of the lesion will reveal new links in its pathogenesis and develop more effective methods of treatment.

Role of Sphingosine 1-Phosphate (S1P) Receptor 1 in Experimental Autoimmune Encephalomyelitis —II

2013 ◽  
Vol 04 (08) ◽  
pp. 638-646 ◽  
Author(s):  
Noriyasu Seki ◽  
Hirotoshi Kataoka ◽  
Kunio Sugahara ◽  
Atsushi Fukunari ◽  
Kenji Chiba
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Autoimmune Encephalomyelitis ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor ◽  
Experimental Autoimmune

The Role of Sphingosine-1-Phosphate (S1P) in Thrombopoiesis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. SCI-54-SCI-54
Author(s):  
Steffen Massberg
Keyword(s):  
Conflicts Of Interest ◽  
Multiphoton Microscopy ◽  
Lipid Mediator ◽  
Severe Thrombocytopenia ◽  
Time Loss ◽  
Sphingosine Kinase 2 ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor

Abstract Human megakaryocytes (MKs) release trillions of platelets each day into the circulation to maintain normal homeostatic platelet levels. However, the signals that control platelet biogenesis in vivo remain incompletely understood. We have recently identified that extracellular sphingosine 1-phosphate (S1P) plays a key role in thrombopoiesis. Using conditional mutants and intravital multiphoton microscopy, we demonstrate that the lipid mediator S1P serves as a critical directional cue guiding the elongation of megakaryocytic proplatelet (PP) extensions from the interstitium into bone marrow sinusoids and triggering the subsequent shedding of PPs into the blood. Correspondingly, mice lacking the S1P receptor S1pr1 develop severe thrombocytopenia caused by both formation of aberrant extravascular PPs and defective intravascular PP shedding. In contrast, activation of S1pr1 signaling leads to the prompt release of new platelets into the circulating blood. In addition to its role as an extracellular mediator, S1P can also function as a second messenger within the intracellular compartment. Correspondingly, we have demonstrated that MKs express the S1P-generating enzyme sphingosine kinase 2 (Sphk2). Sphk2 predominantly localizes to the nucleus and is the major source of intracellular S1P in MKs. Loss of Sphk2 significantly reduced intracellular S1P in MKs and downregulated the expression and activity of Src family kinases (SFKs). At the same time, loss of Sphk2 and inhibition of SFK activity resulted in defective intravascular PP shedding, the final stage of thrombopoiesis. Correspondingly, mice lacking Sphk2 in the hematopoietic system display thrombocytopenia. Collectively, our findings uncover a novel function of S1P as master regulator of efficient thrombopoiesis and might raise new therapeutic options for patients with thrombocytopenia. Disclosures No relevant conflicts of interest to declare.

scholarly journals More than Just an Immunosuppressant: The Emerging Role of FTY720 as a Novel Inducer of ROS and Apoptosis

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Teruaki Takasaki ◽  
Kanako Hagihara ◽  
Ryosuke Satoh ◽  
Reiko Sugiura
Keyword(s):  
Cancer Treatment ◽  
Defense Mechanisms ◽  
Chemotherapeutic Agents ◽  
Future Directions ◽  
Receptor Modulator ◽  
Cystine Transporter ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor ◽  
Fingolimod Hydrochloride

Fingolimod hydrochloride (FTY720) is a first-in-class of sphingosine-1-phosphate (S1P) receptor modulator approved to treat multiple sclerosis by its phosphorylated form (FTY720-P). Recently, a novel role of FTY720 as a potential anticancer drug has emerged. One of the anticancer mechanisms of FTY720 involves the induction of reactive oxygen species (ROS) and subsequent apoptosis, which is largely independent of its property as an S1P modulator. ROS have been considered as a double-edged sword in tumor initiation/progression. Intriguingly, prooxidant therapies have attracted much attention due to its efficacy in cancer treatment. These strategies include diverse chemotherapeutic agents and molecular targeted drugs such as sulfasalazine which inhibits the CD44v-xCT (cystine transporter) axis. In this review, we introduce our recent discoveries using a chemical genomics approach to uncover a signaling network relevant to FTY720-mediated ROS signaling and apoptosis, thereby proposing new potential targets for combination therapy as a means to enhance the antitumor efficacy of FTY720 as a ROS generator. We extend our knowledge by summarizing various measures targeting the vulnerability of cancer cells’ defense mechanisms against oxidative stress. Future directions that may lead to the best use of FTY720 and ROS-targeted strategies as a promising cancer treatment are also discussed.

scholarly journals A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis

2012 ◽  
Vol 209 (12) ◽  
pp. 2165-2181 ◽  
Author(s):  
Lin Zhang ◽  
Martin Orban ◽  
Michael Lorenz ◽  
Verena Barocke ◽  
Daniel Braun ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Multiphoton Microscopy ◽  
Therapeutic Options ◽  
Lipid Mediator ◽  
Severe Thrombocytopenia ◽  
Master Regulator ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor

Millions of platelets are produced each hour by bone marrow (BM) megakaryocytes (MKs). MKs extend transendothelial proplatelet (PP) extensions into BM sinusoids and shed new platelets into the blood. The mechanisms that control platelet generation remain incompletely understood. Using conditional mutants and intravital multiphoton microscopy, we show here that the lipid mediator sphingosine 1-phosphate (S1P) serves as a critical directional cue guiding the elongation of megakaryocytic PP extensions from the interstitium into BM sinusoids and triggering the subsequent shedding of PPs into the blood. Correspondingly, mice lacking the S1P receptor S1pr1 develop severe thrombocytopenia caused by both formation of aberrant extravascular PPs and defective intravascular PP shedding. In contrast, activation of S1pr1 signaling leads to the prompt release of new platelets into the circulating blood. Collectively, our findings uncover a novel function of the S1P–S1pr1 axis as master regulator of efficient thrombopoiesis and might raise new therapeutic options for patients with thrombocytopenia.

scholarly journals Role of Sphingosine 1-Phosphate (S1P) Receptor 1 in Experimental Autoimmune Encephalomyelitis —I

2013 ◽  
Vol 04 (08) ◽  
pp. 628-637 ◽  
Author(s):  
Noriyasu Seki ◽  
Yasuhiro Maeda ◽  
Hirotoshi Kataoka ◽  
Kunio Sugahara ◽  
Kenji Chiba
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Autoimmune Encephalomyelitis ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor ◽  
Experimental Autoimmune

Building a better sphingosine kinase-1 inhibitor

2012 ◽  
Vol 444 (1) ◽  
pp. e1-e2 ◽  
Author(s):  
Kevin R. Lynch
Keyword(s):  
Cancer Progression ◽  
Therapeutic Strategy ◽  
Therapeutic Benefit ◽  
Biochemical Journal ◽  
Molecule Inhibitor ◽  
Sphingosine 1 Phosphate ◽  
Sphingosine Kinases ◽  
S1p Receptor ◽  
Multiple Sclerosis Patients

Sphingosine 1-phosphate (S1P) is currently one of the most intensely studied lipid mediators. Interest in S1P has been propelled by the development of fingolimod, an S1P receptor agonist prodrug, which revealed both a theretofore unsuspected role of S1P in lymphocyte trafficking and that such modulation of the immune system achieves therapeutic benefit in multiple sclerosis patients. S1P is synthesized from sphingosine by two SphKs (sphingosine kinases) (SphK1 and SphK2). Manipulation of SphK levels using molecular biology and mouse genetic tools has implicated these enzymes, particularly SphK1, in a variety of pathological processes such as fibrosis, inflammation and cancer progression. The results of such studies have spurred interest in SphK1 as a drug target. In this issue of the Biochemical Journal, Schnute et al. describe a small molecule inhibitor of SphK1 that is both potent and selective. Such chemical tools are essential to learn whether targeting S1P signalling at the level of synthesis is a viable therapeutic strategy.

scholarly journals Insights into the Pathophysiology of Psychiatric Symptoms in Central Nervous System Disorders: Implications for Early and Differential Diagnosis

2021 ◽  
Vol 22 (9) ◽  
pp. 4440
Author(s):  
Giulia Menculini ◽  
Elena Chipi ◽  
Federico Paolini Paoletti ◽  
Lorenzo Gaetani ◽  
Pasquale Nigro ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Impulse Control ◽  
Psychiatric Symptoms ◽  
Neurological Diseases ◽  
Clinical Manifestations ◽  
Obsessive Compulsive ◽  
Clinical Onset ◽  
Brain Circuits

Different psychopathological manifestations, such as affective, psychotic, obsessive-compulsive symptoms, and impulse control disturbances, may occur in most central nervous system (CNS) disorders including neurodegenerative and neuroinflammatory diseases. Psychiatric symptoms often represent the clinical onset of such disorders, thus potentially leading to misdiagnosis, delay in treatment, and a worse outcome. In this review, psychiatric symptoms observed along the course of several neurological diseases, namely Alzheimer’s disease, fronto-temporal dementia, Parkinson’s disease, Huntington’s disease, and multiple sclerosis, are discussed, as well as the involved brain circuits and molecular/synaptic alterations. Special attention has been paid to the emerging role of fluid biomarkers in early detection of these neurodegenerative diseases. The frequent occurrence of psychiatric symptoms in neurological diseases, even as the first clinical manifestations, should prompt neurologists and psychiatrists to share a common clinico-biological background and a coordinated diagnostic approach.

scholarly journals Role of sphingosine-1-phosphate (S1P) and S1P receptor 2 in the phagocytosis of Cryptococcus neoformans by alveolar macrophages

Microbiology ◽  
2011 ◽  
Vol 157 (5) ◽  
pp. 1416-1427 ◽  
Author(s):  
Travis McQuiston ◽  
Chiara Luberto ◽  
Maurizio Del Poeta
Keyword(s):  
Cryptococcus Neoformans ◽  
Alveolar Macrophages ◽  
Pathogenic Fungus ◽  
Mrna Levels ◽  
Fcγ Receptors ◽  
Sphingosine 1 Phosphate ◽  
Lipid Product ◽  
S1p Receptor ◽  
Extracellular Environment

The pathogenic fungus Cryptococcus neoformans is a major cause of morbidity and mortality in immunocompromised individuals. Infection of the human host occurs through inhalation of infectious propagules following environmental exposure. In the lung, C. neoformans can reside in the extracellular environment of the alveolar spaces or, upon phagocytosis, it can survive and grow intracellularly within alveolar macrophages (AMs). In previous studies, we found that sphingosine kinase 1 (SK1) influenced the intracellular residency of C. neoformans within AMs. Therefore, with this study we aimed to examine the role of the SK1 lipid product, sphingosine-1-phosphate (S1P), in the AMs–C. neoformans interaction. It was found that extracellular S1P enhances the phagocytosis of C. neoformans by AMs. Using both genetic and pharmacological approaches we further show that extracellular S1P exerts its effect on the phagocytosis of C. neoformans by AMs through S1P receptor 2 (S1P2). Interestingly, loss of S1P2 caused a dramatic decrease in the mRNA levels of Fcγ receptors I (FcγRI), -II and -III. In conclusion, our data suggest that extracellular S1P increases antibody-mediated phagocytosis through S1P2 by regulating the expression of the phagocytic Fcγ receptors.

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