{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T05:59:49Z","timestamp":1778392789081,"version":"3.51.4"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001700","name":"MEXT","doi-asserted-by":"publisher","award":["19H02836"],"award-info":[{"award-number":["19H02836"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"MEXT","doi-asserted-by":"publisher","award":["21K05303"],"award-info":[{"award-number":["21K05303"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009029","name":"Adaptable and Seamless Technology Transfer Program through Target-Driven R and D","doi-asserted-by":"publisher","award":["JPMJTM20AB"],"award-info":[{"award-number":["JPMJTM20AB"]}],"id":[{"id":"10.13039\/501100009029","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Sphingolipids (SLs), found in all animals, plants, and fungi and in certain prokaryotic organisms, exhibit essential physiological functions that cannot be replicated by other lipids. Although SLs and their related biomolecules behave as lipid mediators, skin barrier systems, and epitopes, their detailed biological functions have not yet been revealed, unlike those of proteins and nucleic acids, because the biosynthesis of SLs is not governed by the central dogma. Recently, SLs have been widely studied in relation to diseases such as obesity, dementia, and neuron agenesis and have attracted attention as molecules related to unmet medical needs. This review presents the recent applications of the SL chemical biology in unmet medical needs.<\/jats:p>","DOI":"10.1093\/bbb\/zbae166","type":"journal-article","created":{"date-parts":[[2024,12,15]],"date-time":"2024-12-15T23:23:20Z","timestamp":1734305000000},"page":"205-214","source":"Crossref","is-referenced-by-count":4,"title":["Elucidation of physiological functions of sphingolipid-related molecules by chemical approaches"],"prefix":"10.1093","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9115-6478","authenticated-orcid":false,"given":"Yuta","family":"Murai","sequence":"first","affiliation":[{"name":"Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University , Sapporo, Hokkaido ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,12,17]]},"reference":[{"key":"2026041420222984400_bib1","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/S0959-440X(02)00376-7","article-title":"Lubricating cell signaling pathwaysvwith gangliosides","volume":"12","author":"Allende","year":"2002","journal-title":"Curr Opin Struct Biol"},{"key":"2026041420222984400_bib2","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1023\/A:1022445130743","article-title":"The role of globo-series glycolipids in neuronal cell differentiation\u2014a review","volume":"23","author":"Ariga","year":"1998","journal-title":"Neurochem Res"},{"key":"2026041420222984400_bib3","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1016\/j.pharep.2015.12.008","article-title":"Regulation of sphingomyelin metabolism","volume":"68","author":"Bienias","year":"2016","journal-title":"Pharmacol Rep"},{"key":"2026041420222984400_bib4","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/0165-3806(88)90075-2","article-title":"Comparison of epi-GM3 with GM3 and GM1 as stimulators of neurite outgrowth","volume":"39","author":"Cannella","year":"1988","journal-title":"Dev Brain Res"},{"key":"2026041420222984400_bib5","doi-asserted-by":"publisher","first-page":"pl6","DOI":"10.1126\/stke.2002.129.pl6","article-title":"Protein lipid overlay assay","volume":"2002","author":"Dowler","year":"2002","journal-title":"Sci STKE"},{"key":"2026041420222984400_bib6","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1161\/ATVBAHA.110.213363","article-title":"Selective reduction in the sphingomyelin content of atherogenic lipoproteins inhibits their retention in murine aortas and the subsequent development of atherosclerosis","volume":"30","author":"Fan","year":"2010","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2026041420222984400_bib7","doi-asserted-by":"publisher","first-page":"7351","DOI":"10.1073\/pnas.85.19.7351","article-title":"Gangliosides prevent glutamate and kainate neurotoxicity in primary neuronal cultures of neonatal rat cerebellum and Cortex","volume":"85","author":"Favaron","year":"1988","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026041420222984400_bib8","doi-asserted-by":"publisher","first-page":"208","DOI":"10.7164\/antibiotics.47.208","article-title":"Fungal metabolites. Part 11. A potent immunosuppressive activity found in Isaria sinclairii metabolite","volume":"47","author":"Fujita","year":"1994","journal-title":"J Antibiot"},{"key":"2026041420222984400_bib9","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1023\/A:1011086929064","article-title":"Traveling for the glycosphingolipid path","volume":"17","author":"Hakomori","year":"2000","journal-title":"Glycoconj J"},{"key":"2026041420222984400_bib10","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/S1388-1981(03)00059-3","article-title":"Serine palmitoyltransferase, a key enzyme of sphingolipid metabolism","volume":"1632","author":"Hanada","year":"2003","journal-title":"Biochim Biophys Acta"},{"key":"2026041420222984400_bib11","doi-asserted-by":"publisher","first-page":"1855","DOI":"10.1126\/science.274.5294.1855","article-title":"Functions of ceramide in coordinating cellular responses to stress","volume":"274","author":"Hannun","year":"1996","journal-title":"Science"},{"key":"2026041420222984400_bib12","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1089\/biores.2013.0008","article-title":"Inducing neurite outgrowth by mechanical cell stretch","volume":"2","author":"Higgins","year":"2013","journal-title":"Biores Open Access"},{"key":"2026041420222984400_bib13","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/sj.emboj.7600034","article-title":"Identification of a family of animal sphingomyelin synthases","volume":"23","author":"Huitema","year":"2004","journal-title":"EMBO J"},{"key":"2026041420222984400_bib14","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.clim.2011.05.005","article-title":"Fingolimod in multiple sclerosis: mechanisms of action and clinical efficacy","volume":"142","author":"Ingwersen","year":"2012","journal-title":"Clin Immunol"},{"key":"2026041420222984400_bib15","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1007\/s10719-013-9516-4","article-title":"GM3 and diabetes","volume":"31","author":"Inokuchi","year":"2014","journal-title":"Glycoconj J"},{"key":"2026041420222984400_bib16","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1093\/glycob\/11.2.125","article-title":"Specificity of carbohydrate structures of gangliosides in the activity to regenerate the rat axotomized hypoglossal","volume":"11","author":"Itoh","year":"2001","journal-title":"Glycobiology"},{"key":"2026041420222984400_bib17","doi-asserted-by":"publisher","first-page":"e101732","DOI":"10.15252\/embj.2019101732","article-title":"Homeostatic and pathogenic roles of GM3 ganglioside molecular species in TLR4 signaling in obesity","volume":"39","author":"Kanoh","year":"2020","journal-title":"EMBO J"},{"key":"2026041420222984400_bib18","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1002\/chir.23179","article-title":"Chiral combinatorial preparation and biological evaluation of unique ceramides for inhibition of sphingomyelin synthase","volume":"32","author":"Koolath","year":"2020","journal-title":"Chirality"},{"key":"2026041420222984400_bib19","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1021\/acsmedchemlett.3c00252","article-title":"Stereochemistry of sphingolipids in ganglioside GM3 enhances recovery of nervous functionality","volume":"14","author":"Koolath","year":"2023","journal-title":"ACS Med Chem Lett"},{"key":"2026041420222984400_bib20","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1161\/ATVBAHA.112.251538","article-title":"Impact of sphingomyelin synthase 1 deficiency on sphingolipid metabolism and atherosclerosis in mice","volume":"32","author":"Li","year":"2012","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2026041420222984400_bib21","doi-asserted-by":"publisher","first-page":"4029","DOI":"10.1113\/jphysiol.2012.235846","article-title":"Deficiency of sphingomyelin synthase-1 but not sphingomyelin synthase-2 causes hearing impairments in mice","volume":"590","author":"Lu","year":"2012","journal-title":"J Physiol"},{"key":"2026041420222984400_bib22","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1016\/S0531-5565(02)00138-9","article-title":"GD3 in cellular ageing and apoptosis","volume":"37","author":"Malisan","year":"2002","journal-title":"Exp Gerontol"},{"key":"2026041420222984400_bib23","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/S1388-1981(02)00339-6","article-title":"GD3 ganglioside and apoptosis","volume":"1585","author":"Malisan","year":"2002","journal-title":"Biochim Biophys Acta"},{"key":"2026041420222984400_bib24","doi-asserted-by":"publisher","first-page":"1774","DOI":"10.1126\/science.1197623","article-title":"Decreased clearance of CNS beta-amyloid in Alzheimer's disease","volume":"330","author":"Mawuenyega","year":"2010","journal-title":"Science"},{"key":"2026041420222984400_bib25","doi-asserted-by":"publisher","first-page":"re15","DOI":"10.1126\/stke.2002.160.re15","article-title":"Regulation of growth factor receptors by gangliosides","volume":"2002","author":"Miljan","year":"2002","journal-title":"Sci STKE"},{"key":"2026041420222984400_bib26","doi-asserted-by":"publisher","first-page":"28544","DOI":"10.1074\/jbc.M111.255646","article-title":"Dynamic modification of sphingomyelin in lipid microdomains controls development of obesity, fatty liver, and type 2 diabetes","volume":"286","author":"Mitsutake","year":"2011","journal-title":"J Biol Chem"},{"key":"2026041420222984400_bib27","doi-asserted-by":"publisher","first-page":"10751","DOI":"10.3390\/ijms231810751","article-title":"Evaluation of plant ceramide species-induced exosome release from neuronal cells and exosome loading using deuterium chemistry","volume":"23","author":"Murai","year":"2022","journal-title":"Int J Mol Sci"},{"key":"2026041420222984400_bib28","doi-asserted-by":"publisher","first-page":"105202","DOI":"10.1016\/j.chemphyslip.2022.105202","article-title":"Penta-deuterium-labeled 4E, 8Z-sphingadienine for rapid analysis in sphingolipidomics study","volume":"245","author":"Murai","year":"2022","journal-title":"Chem Phys Lipids"},{"key":"2026041420222984400_bib29","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/S0361-090X(02)00033-8","article-title":"Glycotherapy for cancer: remodeling of ganglioside pattern as an effective approach for cancer therapy","volume":"26","author":"Nojiri","year":"2002","journal-title":"Cancer Detect Prev"},{"key":"2026041420222984400_bib30","doi-asserted-by":"publisher","first-page":"3816","DOI":"10.1096\/fj.201601225RR","article-title":"Sphingomyelin synthase 2 deficiency inhibits the induction of murine colitis-associated colon cancer","volume":"31","author":"Ohnishi","year":"2017","journal-title":"FASEB J"},{"key":"2026041420222984400_bib31","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1111\/j.1365-2443.2009.01319.x","article-title":"Palmitoylation of the sphingosine 1-phosphate receptor S1P is involved in its signaling functions and internalization","volume":"14","author":"Ohno","year":"2009","journal-title":"Genes Cells"},{"key":"2026041420222984400_bib32","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1021\/acsmedchemlett.9b00171","article-title":"Malabaricone C as natural sphingomyelin synthase inhibitor against diet-induced obesity and its lipid metabolism in mice","volume":"10","author":"Othman","year":"2019","journal-title":"ACS Med Chem Lett"},{"key":"2026041420222984400_bib33","doi-asserted-by":"publisher","first-page":"20916","DOI":"10.1074\/jbc.274.30.20916","article-title":"Glycosphingolipidenriched signaling domain in mouse neuroblastoma Neuro2a cells. Mechanism of ganglioside-dependent neuritogenesis","volume":"274","author":"Prinetti","year":"1999","journal-title":"J Biol Chem"},{"key":"2026041420222984400_bib34","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1111\/j.1749-6632.1998.tb09678.x","article-title":"The semisynthetic glycosphingolipid LIGA20 potently protects neurons against apoptosis","volume":"845","author":"Saito","year":"1998","journal-title":"Ann NY Acad Sci"},{"key":"2026041420222984400_bib35","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1038\/nature19323","article-title":"The antibody aducanumab reduces a\u03b2 plaques in Alzheimer\u2019s disease","volume":"537","author":"Sevigny","year":"2016","journal-title":"Nature"},{"key":"2026041420222984400_bib36","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.jalz.2011.03.003","article-title":"Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer's disease","volume":"7","author":"Sperling","year":"2011","journal-title":"Alzheimer\u2019s Dement"},{"key":"2026041420222984400_bib37","doi-asserted-by":"publisher","first-page":"12758","DOI":"10.1039\/C8CC05595E","article-title":"Structure-inspired design of a sphingolipid mimic sphingosine-1-phosphate receptor agonist from a naturally occurring sphingomyelin synthase inhibitor","volume":"54","author":"Swamy","year":"2018","journal-title":"Chem Commun"},{"key":"2026041420222984400_bib38","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1016\/j.bbalip.2013.12.003","article-title":"The role of sphingomyelin and sphingomyelin synthases in cell death, proliferation and migration\u2014from cell and animal models to human disorders","volume":"1841","author":"Taniguchi","year":"2014","journal-title":"Biochim Biophys Acta"},{"key":"2026041420222984400_bib39","doi-asserted-by":"publisher","first-page":"25512","DOI":"10.1074\/jbc.M202947200","article-title":"Identification and characterization of a sphingolipid delta 4-desaturase family","volume":"277","author":"Ternes","year":"2002","journal-title":"J Biol Chem"},{"key":"2026041420222984400_bib40","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1056\/NEJMoa2212948","article-title":"Lecanemab in early Alzheimer\u2019s disease","volume":"388","author":"van\u00a0Dyck","year":"2023","journal-title":"N Engl J Med"},{"key":"2026041420222984400_bib41","doi-asserted-by":"publisher","first-page":"18688","DOI":"10.1074\/jbc.M401205200","article-title":"Expression cloning of a human cDNA restoring sphingomyelin synthesis and cell growth in sphingomyelin synthase-defective lymphoid cells","volume":"279","author":"Yamaoka","year":"2004","journal-title":"J Biol Chem"},{"key":"2026041420222984400_bib42","doi-asserted-by":"publisher","first-page":"3992","DOI":"10.1074\/jbc.M110.179176","article-title":"Mitochondrial dysfunction and increased reactive oxygen species impair insulin secretion in sphingomyelin synthase 1-null mice","volume":"286","author":"Yano","year":"2011","journal-title":"J Biol Chem"},{"key":"2026041420222984400_bib43","doi-asserted-by":"publisher","first-page":"16022","DOI":"10.1096\/fj.202001599R","article-title":"Lysosomal-associated transmembrane protein 4B regulates ceramide-induced exosome release","volume":"34","author":"Yuyama","year":"2020","journal-title":"FASEB J"},{"key":"2026041420222984400_bib44","doi-asserted-by":"publisher","first-page":"10977","DOI":"10.1074\/jbc.M111.324616","article-title":"Sphingolipid-modulated exosome secretion promotes clearance of amyloid-\u03b2 by microglia","volume":"287","author":"Yuyama","year":"2012","journal-title":"J Biol Chem"},{"key":"2026041420222984400_bib45","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1016\/j.chemphyslip.2012.09.003","article-title":"A sensitive cell-based method to screen for selective inhibitors of SMS1 or SMS2 using HPLC and a fluorescent substrate","volume":"165","author":"Zama","year":"2012","journal-title":"Chem Phys Lipids"},{"key":"2026041420222984400_bib46","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.bcp.2011.04.009","article-title":"The effect of sphingomyelin synthase 2 (SMS2) deficiency on the expression of drug transporters inmouse brain","volume":"82","author":"Zhang","year":"2011","journal-title":"Biochem Pharmacol"},{"key":"2026041420222984400_bib47","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1016\/j.ejmech.2018.01.079","article-title":"Chemoenzymatically synthesized GM3 analogues as potential therapeutic agents to recover nervous functionality after injury by inducing neurite outgrowth","volume":"146","author":"Zheng","year":"2018","journal-title":"Eur J Med Chem"}],"container-title":["Bioscience, Biotechnology, and Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bbb\/advance-article-pdf\/doi\/10.1093\/bbb\/zbae166\/61218711\/zbae166.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bbb\/article-pdf\/89\/2\/205\/61218711\/zbae166.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bbb\/article-pdf\/89\/2\/205\/61218711\/zbae166.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:44:19Z","timestamp":1776213859000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bbb\/article\/89\/2\/205\/7926969"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,17]]},"references-count":47,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,12,17]]},"published-print":{"date-parts":[[2025,1,24]]}},"URL":"https:\/\/doi.org\/10.1093\/bbb\/zbae166","relation":{},"ISSN":["1347-6947"],"issn-type":[{"value":"1347-6947","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,2]]},"published":{"date-parts":[[2024,12,17]]}}}