Sphingosine-1-Phosphate (S1P) and S1P Signaling Pathway: Therapeutic Targets in Autoimmunity and Inflammation
Sphingosine-1-phosphate (S1P) and S1P receptors (S1PR) are ubiquitously expressed. S1P-S1PR signaling has been well characterized in immune trafficking and activation in innate and adaptive immune systems. However, the full extent of its involvement in the pathogenesis of autoimmune diseases is not...
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| Veröffentlicht in: | Drugs (New York, N.Y.) N.Y.), 2016-07, Vol.76 (11), p.1067-1079 |
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| description | Sphingosine-1-phosphate (S1P) and S1P receptors (S1PR) are ubiquitously expressed. S1P-S1PR signaling has been well characterized in immune trafficking and activation in innate and adaptive immune systems. However, the full extent of its involvement in the pathogenesis of autoimmune diseases is not well understood. FTY720 (fingolimod), a non-selective S1PR modulator, significantly decreased annualized relapse rates in relapsing-remitting multiple sclerosis (MS). FTY720, which primarily targets S1P receptor 1 as a functional antagonist, arrests lymphocyte egress from secondary lymphoid tissues and reduces neuroinflammation in the central nervous system (CNS). Recent studies suggest that FTY720 also decreases astrogliosis and promotes oligodendrocyte differentiation within the CNS and may have therapeutic benefit to prevent brain atrophy. Since S1P signaling is involved in multiple immune functions, therapies targeting S1P axis may be applicable to treat autoimmune diseases other than MS. Currently, over a dozen selective S1PR and S1P pathway modulators with potentially superior therapeutic efficacy and better side-effect profiles are in the pipeline of drug development. Furthermore, newly characterized molecules such as apolipoprotein M (ApoM) (S1P chaperon) and SPNS2 (S1P transporter) are also potential targets for treatment of autoimmune diseases. Finally, the application of therapies targeting S1P and S1P signaling pathways may be expanded to treat several other immune-mediated disorders (such as post-infectious diseases, post-stroke and post-stroke dementia) and inflammatory conditions beyond their application in primary autoimmune diseases. |
| doi_str_mv | 10.1007/s40265-016-0603-2 |
| format | Article |
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S1P-S1PR signaling has been well characterized in immune trafficking and activation in innate and adaptive immune systems. However, the full extent of its involvement in the pathogenesis of autoimmune diseases is not well understood. FTY720 (fingolimod), a non-selective S1PR modulator, significantly decreased annualized relapse rates in relapsing-remitting multiple sclerosis (MS). FTY720, which primarily targets S1P receptor 1 as a functional antagonist, arrests lymphocyte egress from secondary lymphoid tissues and reduces neuroinflammation in the central nervous system (CNS). Recent studies suggest that FTY720 also decreases astrogliosis and promotes oligodendrocyte differentiation within the CNS and may have therapeutic benefit to prevent brain atrophy. Since S1P signaling is involved in multiple immune functions, therapies targeting S1P axis may be applicable to treat autoimmune diseases other than MS. Currently, over a dozen selective S1PR and S1P pathway modulators with potentially superior therapeutic efficacy and better side-effect profiles are in the pipeline of drug development. Furthermore, newly characterized molecules such as apolipoprotein M (ApoM) (S1P chaperon) and SPNS2 (S1P transporter) are also potential targets for treatment of autoimmune diseases. Finally, the application of therapies targeting S1P and S1P signaling pathways may be expanded to treat several other immune-mediated disorders (such as post-infectious diseases, post-stroke and post-stroke dementia) and inflammatory conditions beyond their application in primary autoimmune diseases.</description><identifier>ISSN: 0012-6667</identifier><identifier>EISSN: 1179-1950</identifier><identifier>DOI: 10.1007/s40265-016-0603-2</identifier><identifier>PMID: 27318702</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Animals ; Apolipoproteins ; Autoimmune diseases ; Autoimmune Diseases - drug therapy ; Autoimmune Diseases - metabolism ; Disease ; Enzymes ; Fingolimod Hydrochloride - pharmacology ; Fingolimod Hydrochloride - therapeutic use ; Homeostasis ; Humans ; Inflammation - drug therapy ; Inflammation - metabolism ; Internal Medicine ; Kinases ; Leading Article ; Lymphatic system ; Lymphocytes ; Lymphocytes - drug effects ; Lysophospholipids - antagonists & inhibitors ; Lysophospholipids - metabolism ; Medicine ; Medicine & Public Health ; Molecular Targeted Therapy - methods ; Multiple sclerosis ; Pharmacology/Toxicology ; Pharmacotherapy ; Phosphorylation ; Receptors, Lysosphingolipid - metabolism ; Signal Transduction - drug effects ; Sphingosine - analogs & derivatives ; Sphingosine - antagonists & inhibitors ; Sphingosine - metabolism ; Thymus gland ; Tumor necrosis factor-TNF</subject><ispartof>Drugs (New York, N.Y.), 2016-07, Vol.76 (11), p.1067-1079</ispartof><rights>Springer International Publishing Switzerland 2016</rights><rights>Copyright Springer Science & Business Media Jul 2016</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c471t-c96f24630166900cb26f43f3036226f91cc9c2a945c1cba2a33010ace722dfc03</citedby><cites>FETCH-LOGICAL-c471t-c96f24630166900cb26f43f3036226f91cc9c2a945c1cba2a33010ace722dfc03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s40265-016-0603-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s40265-016-0603-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27318702$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tsai, Hsing-Chuan</creatorcontrib><creatorcontrib>Han, May H.</creatorcontrib><title>Sphingosine-1-Phosphate (S1P) and S1P Signaling Pathway: Therapeutic Targets in Autoimmunity and Inflammation</title><title>Drugs (New York, N.Y.)</title><addtitle>Drugs</addtitle><addtitle>Drugs</addtitle><description>Sphingosine-1-phosphate (S1P) and S1P receptors (S1PR) are ubiquitously expressed. S1P-S1PR signaling has been well characterized in immune trafficking and activation in innate and adaptive immune systems. However, the full extent of its involvement in the pathogenesis of autoimmune diseases is not well understood. FTY720 (fingolimod), a non-selective S1PR modulator, significantly decreased annualized relapse rates in relapsing-remitting multiple sclerosis (MS). FTY720, which primarily targets S1P receptor 1 as a functional antagonist, arrests lymphocyte egress from secondary lymphoid tissues and reduces neuroinflammation in the central nervous system (CNS). Recent studies suggest that FTY720 also decreases astrogliosis and promotes oligodendrocyte differentiation within the CNS and may have therapeutic benefit to prevent brain atrophy. Since S1P signaling is involved in multiple immune functions, therapies targeting S1P axis may be applicable to treat autoimmune diseases other than MS. Currently, over a dozen selective S1PR and S1P pathway modulators with potentially superior therapeutic efficacy and better side-effect profiles are in the pipeline of drug development. Furthermore, newly characterized molecules such as apolipoprotein M (ApoM) (S1P chaperon) and SPNS2 (S1P transporter) are also potential targets for treatment of autoimmune diseases. Finally, the application of therapies targeting S1P and S1P signaling pathways may be expanded to treat several other immune-mediated disorders (such as post-infectious diseases, post-stroke and post-stroke dementia) and inflammatory conditions beyond their application in primary autoimmune diseases.</description><subject>Animals</subject><subject>Apolipoproteins</subject><subject>Autoimmune diseases</subject><subject>Autoimmune Diseases - drug therapy</subject><subject>Autoimmune Diseases - metabolism</subject><subject>Disease</subject><subject>Enzymes</subject><subject>Fingolimod Hydrochloride - pharmacology</subject><subject>Fingolimod Hydrochloride - therapeutic use</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Inflammation - drug therapy</subject><subject>Inflammation - metabolism</subject><subject>Internal Medicine</subject><subject>Kinases</subject><subject>Leading Article</subject><subject>Lymphatic system</subject><subject>Lymphocytes</subject><subject>Lymphocytes - drug effects</subject><subject>Lysophospholipids - antagonists & inhibitors</subject><subject>Lysophospholipids - metabolism</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Molecular Targeted Therapy - methods</subject><subject>Multiple sclerosis</subject><subject>Pharmacology/Toxicology</subject><subject>Pharmacotherapy</subject><subject>Phosphorylation</subject><subject>Receptors, Lysosphingolipid - metabolism</subject><subject>Signal Transduction - drug effects</subject><subject>Sphingosine - analogs & derivatives</subject><subject>Sphingosine - antagonists & inhibitors</subject><subject>Sphingosine - metabolism</subject><subject>Thymus gland</subject><subject>Tumor necrosis factor-TNF</subject><issn>0012-6667</issn><issn>1179-1950</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNkUFr3DAQhUVpaLZJf0AvRdBLclCjkWzJ6i2Epg0EsrDbs9Bq5bWCLbuSTNh_X202LaVQ6Ekj5ntvmHkIvQf6CSiVV6miTNSEgiBUUE7YK7QAkIqAqulrtKAUGBFCyFP0NqXHw1fV6g06ZZJDIylboGE1dT7sxuSDI0CW3ZimzmSHL1awvMQmbHEp8MrvgukLiJcmd09m_xmvOxfN5ObsLV6buHM5YR_w9ZxHPwxz8Hn_LL8LbW-GwWQ_hnN00po-uXcv7xn6fvtlffON3D98vbu5vie2kpCJVaJlleBlMaEotRsm2oq3nHLBSqnAWmWZUVVtwW4MM7yg1FgnGdu2lvIzdHH0neL4Y3Yp68En6_reBDfOSUPDZNNUTIn_QCmT5c68LujHv9DHcY7lLs-GTEADQhUKjpSNY0rRtXqKfjBxr4HqQ2z6GJsu2-lDbJoVzYcX53kzuO1vxa-cCsCOQCqtsHPxj9H_dP0JZ6ugJw</recordid><startdate>20160701</startdate><enddate>20160701</enddate><creator>Tsai, Hsing-Chuan</creator><creator>Han, May H.</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>4T-</scope><scope>7QO</scope><scope>7RV</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7T5</scope></search><sort><creationdate>20160701</creationdate><title>Sphingosine-1-Phosphate (S1P) and S1P Signaling Pathway: Therapeutic Targets in Autoimmunity and Inflammation</title><author>Tsai, Hsing-Chuan ; Han, May H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c471t-c96f24630166900cb26f43f3036226f91cc9c2a945c1cba2a33010ace722dfc03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Apolipoproteins</topic><topic>Autoimmune diseases</topic><topic>Autoimmune Diseases - drug therapy</topic><topic>Autoimmune Diseases - metabolism</topic><topic>Disease</topic><topic>Enzymes</topic><topic>Fingolimod Hydrochloride - pharmacology</topic><topic>Fingolimod Hydrochloride - therapeutic use</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Inflammation - drug therapy</topic><topic>Inflammation - metabolism</topic><topic>Internal Medicine</topic><topic>Kinases</topic><topic>Leading Article</topic><topic>Lymphatic system</topic><topic>Lymphocytes</topic><topic>Lymphocytes - drug effects</topic><topic>Lysophospholipids - antagonists & inhibitors</topic><topic>Lysophospholipids - metabolism</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Molecular Targeted Therapy - methods</topic><topic>Multiple sclerosis</topic><topic>Pharmacology/Toxicology</topic><topic>Pharmacotherapy</topic><topic>Phosphorylation</topic><topic>Receptors, Lysosphingolipid - metabolism</topic><topic>Signal Transduction - drug effects</topic><topic>Sphingosine - analogs & derivatives</topic><topic>Sphingosine - antagonists & inhibitors</topic><topic>Sphingosine - metabolism</topic><topic>Thymus gland</topic><topic>Tumor necrosis factor-TNF</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tsai, Hsing-Chuan</creatorcontrib><creatorcontrib>Han, May H.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Docstoc</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><jtitle>Drugs (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tsai, Hsing-Chuan</au><au>Han, May H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sphingosine-1-Phosphate (S1P) and S1P Signaling Pathway: Therapeutic Targets in Autoimmunity and Inflammation</atitle><jtitle>Drugs (New York, N.Y.)</jtitle><stitle>Drugs</stitle><addtitle>Drugs</addtitle><date>2016-07-01</date><risdate>2016</risdate><volume>76</volume><issue>11</issue><spage>1067</spage><epage>1079</epage><pages>1067-1079</pages><issn>0012-6667</issn><eissn>1179-1950</eissn><abstract>Sphingosine-1-phosphate (S1P) and S1P receptors (S1PR) are ubiquitously expressed. S1P-S1PR signaling has been well characterized in immune trafficking and activation in innate and adaptive immune systems. However, the full extent of its involvement in the pathogenesis of autoimmune diseases is not well understood. FTY720 (fingolimod), a non-selective S1PR modulator, significantly decreased annualized relapse rates in relapsing-remitting multiple sclerosis (MS). FTY720, which primarily targets S1P receptor 1 as a functional antagonist, arrests lymphocyte egress from secondary lymphoid tissues and reduces neuroinflammation in the central nervous system (CNS). Recent studies suggest that FTY720 also decreases astrogliosis and promotes oligodendrocyte differentiation within the CNS and may have therapeutic benefit to prevent brain atrophy. Since S1P signaling is involved in multiple immune functions, therapies targeting S1P axis may be applicable to treat autoimmune diseases other than MS. Currently, over a dozen selective S1PR and S1P pathway modulators with potentially superior therapeutic efficacy and better side-effect profiles are in the pipeline of drug development. Furthermore, newly characterized molecules such as apolipoprotein M (ApoM) (S1P chaperon) and SPNS2 (S1P transporter) are also potential targets for treatment of autoimmune diseases. Finally, the application of therapies targeting S1P and S1P signaling pathways may be expanded to treat several other immune-mediated disorders (such as post-infectious diseases, post-stroke and post-stroke dementia) and inflammatory conditions beyond their application in primary autoimmune diseases.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>27318702</pmid><doi>10.1007/s40265-016-0603-2</doi><tpages>13</tpages></addata></record> |
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| ispartof | Drugs (New York, N.Y.), 2016-07, Vol.76 (11), p.1067-1079 |
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| subjects | Animals Apolipoproteins Autoimmune diseases Autoimmune Diseases - drug therapy Autoimmune Diseases - metabolism Disease Enzymes Fingolimod Hydrochloride - pharmacology Fingolimod Hydrochloride - therapeutic use Homeostasis Humans Inflammation - drug therapy Inflammation - metabolism Internal Medicine Kinases Leading Article Lymphatic system Lymphocytes Lymphocytes - drug effects Lysophospholipids - antagonists & inhibitors Lysophospholipids - metabolism Medicine Medicine & Public Health Molecular Targeted Therapy - methods Multiple sclerosis Pharmacology/Toxicology Pharmacotherapy Phosphorylation Receptors, Lysosphingolipid - metabolism Signal Transduction - drug effects Sphingosine - analogs & derivatives Sphingosine - antagonists & inhibitors Sphingosine - metabolism Thymus gland Tumor necrosis factor-TNF |
| title | Sphingosine-1-Phosphate (S1P) and S1P Signaling Pathway: Therapeutic Targets in Autoimmunity and Inflammation |
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