{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T18:33:25Z","timestamp":1792521205587,"version":"4.5.0"},"reference-count":52,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T00:00:00Z","timestamp":1666742400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation (NRF)","doi-asserted-by":"publisher","award":["2020M3E5D9080660"],"award-info":[{"award-number":["2020M3E5D9080660"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>O-cyclic phytosphingosine-1-phosphate (cPS1P) is a novel and chemically synthesized sphingosine metabolite derived from phytosphingosine-1-phosphate (S1P). This study was undertaken to unveil the potential neuroprotective effects of cPS1P on two different mouse models of Parkinson\u2019s disease (PD). The study used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and neuron specific enolase promoter human alpha-synuclein (NSE-h\u03b1Syn) Korl transgenic mice. MPTP was injected for five consecutive days and cPS1P was injected for alternate days for six weeks intraperitoneally. We performed behavioral tests and analyzed the immunohistochemistry and immunofluorescence staining in the substantia nigra pars compacta (SNpc) and the striatum. The behavior tests showed a significant reduction in the motor functions in the PD models, which was reversed with the administration of cPS1P. In addition, both PD-models showed reduced expression of the sphingosine-1-phosphate receptor 1 (S1PR1), and \u03b1-Syn which was restored with cPS1P treatment. In addition, administration of cPS1P restored dopamine-related proteins such as tyrosine hydroxylase (TH), vesicular monoamine transporter 2 (VMAT2), and dopamine transporter (DAT). Lastly, neuroinflammatory related markers such as glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter protein-1 (Iba-1), c-Jun N-terminal kinases (JNK), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), tumor necrosis factor-alpha (TNF-\u03b1), and interleukin 1 beta (IL-1\u03b2) were all reduced after cPS1P administration. The overall findings supported the notion that cPS1P protects against dopamine depletion, neuroinflammation, and PD-associated symptoms.<\/jats:p>","DOI":"10.3390\/antiox11112107","type":"journal-article","created":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T05:11:33Z","timestamp":1666761093000},"page":"2107","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["O-Cyclic Phytosphingosine-1-Phosphate Protects against Motor Dysfunctions and Glial Cell Mediated Neuroinflammation in the Parkinson\u2019s Disease Mouse Models"],"prefix":"10.3390","volume":"11","author":[{"given":"Hyeon Jin","family":"Lee","sequence":"first","affiliation":[{"name":"Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9150-0155","authenticated-orcid":false,"given":"Kyonghwan","family":"Choe","sequence":"additional","affiliation":[{"name":"Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea"},{"name":"Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, 6229ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Sung","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6248-167X","authenticated-orcid":false,"given":"Amjad","family":"Khan","sequence":"additional","affiliation":[{"name":"Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Woo","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Ju","family":"Park","sequence":"additional","affiliation":[{"name":"Haemato-oncology\/Systems Medicine Group, Paul O\u2019Gorman Leukaemia Research Centre, Institute of Cancer Sciences, College of Medical, Veterinary & Life Sciences (MVLS), University of Glasgow, Glasgow G12 0ZD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myeong Ok","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea"},{"name":"Alz-Dementia Korea Co., Jinju 52828, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1146\/annurev.neuro.28.061604.135718","article-title":"Molecular pathophysiology of Parkinson\u2019s disease","volume":"28","author":"Moore","year":"2005","journal-title":"Annu. 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