{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T03:21:09Z","timestamp":1791429669508,"version":"4.3.3"},"reference-count":52,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T00:00:00Z","timestamp":1641427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["\u2116 075-15-2020-795, \u2116 13.1902.21.0027, RF-190220X0027"],"award-info":[{"award-number":["\u2116 075-15-2020-795, \u2116 13.1902.21.0027, RF-190220X0027"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is a neurodegenerative disease incurable due to late diagnosis and treatment. Therefore, one of the priorities of neurology is to study the mechanisms of PD pathogenesis at the preclinical and early clinical stages. Given the important role of sphingolipids in the pathogenesis of neurodegenerative diseases, we aimed to analyze the gene expression of key sphingolipid metabolism enzymes (ASAH1, ASAH2, CERS1, CERS3, CERS5, GBA1, SMPD1, SMPD2, UGCG) and the content of 32 sphingolipids (subspecies of ceramides, sphingomyelins, monohexosylceramides and sphinganine, sphingosine, and sphingosine-1-phosphate) in the nigrostriatal system in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse models of the preclinical and clinical stages of PD. It has been shown that in PD models, the expression of five of the nine studied genes (CERS1, CERS5, ASAH1, ASAH2, and GBA1) increases but only in the substantia nigra (SN) containing dopaminergic cell bodies. Changes in the expression of enzyme genes were accompanied by an increase in the content of 7 of the 32 studied sphingolipids. Such findings suggest these genes as attractive candidates for diagnostic purposes for preclinical and clinical stages of PD.<\/jats:p>","DOI":"10.3390\/biom12010093","type":"journal-article","created":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T01:15:26Z","timestamp":1641518126000},"page":"93","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The Sphingolipid Asset Is Altered in the Nigrostriatal System of Mice Models of Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9074-7279","authenticated-orcid":false,"given":"Victor","family":"Blokhin","sequence":"first","affiliation":[{"name":"Laboratory of Neural and Neuroendocrine Regulations, Koltzov Institute of Developmental Biology of the Russian Academy of Sciences, 119334 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Shupik","sequence":"additional","affiliation":[{"name":"Institute of Biochemical Physics Named after N.M. Emanuel of the Russian Academy of Sciences, 119334 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulyana","family":"Gutner","sequence":"additional","affiliation":[{"name":"Institute of Biochemical Physics Named after N.M. Emanuel of the Russian Academy of Sciences, 119334 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Pavlova","sequence":"additional","affiliation":[{"name":"Laboratory of Neural and Neuroendocrine Regulations, Koltzov Institute of Developmental Biology of the Russian Academy of Sciences, 119334 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6459-9484","authenticated-orcid":false,"given":"Albert T.","family":"Lebedev","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Maloshitskaya","sequence":"additional","affiliation":[{"name":"Institute of Biochemical Physics Named after N.M. Emanuel of the Russian Academy of Sciences, 119334 Moscow, Russia"},{"name":"Department of Organic Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vsevolod","family":"Bogdanov","sequence":"additional","affiliation":[{"name":"Laboratory of Neural and Neuroendocrine Regulations, Koltzov Institute of Developmental Biology of the Russian Academy of Sciences, 119334 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Sokolov","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Alessenko","sequence":"additional","affiliation":[{"name":"Institute of Biochemical Physics Named after N.M. 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Am. Med. Assoc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1111\/cns.13429","article-title":"Development of early diagnosis of Parkinson\u2019s disease: Illusion or reality?","volume":"26","author":"Ugrumov","year":"2020","journal-title":"CNS Neurosci. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1002\/ana.21995","article-title":"Clinical Progression in Parkinson\u2019s Disease and the Neurobiology of Axons","volume":"67","author":"Cheng","year":"2010","journal-title":"Ann. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"293","DOI":"10.3389\/fncel.2016.00293","article-title":"Early Degeneration of Both Dopaminergic and Serotonergic Axons\u2014A Common Mechanism in Parkinson\u2019s Disease","volume":"10","author":"Grosch","year":"2016","journal-title":"Front. Cell. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"395","DOI":"10.3389\/fneur.2020.00395","article-title":"Clinical and Imaging Markers of Prodromal Parkinson\u2019s Disease","volume":"11","author":"Hustad","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"a009399","DOI":"10.1101\/cshperspect.a009399","article-title":"\u03b1-Synuclein in Parkinson\u2019s Disease","volume":"2","author":"Stefanis","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40035-015-0042-0","article-title":"Neuroinflammation in Parkinson\u2019s disease and its potential as therapeutic target","volume":"4","author":"Wang","year":"2015","journal-title":"Transl. Neurodegener."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.tem.2018.11.003","article-title":"Sphingolipids in the Pathogenesis of Parkinson\u2019s Disease and Parkin-sonism","volume":"30","author":"Lin","year":"2019","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Xicoy, H., Wieringa, B., and Martens, G.J.M. (2019). The Role of Lipids in Parkinson\u2019s Disease. Cells, 8.","DOI":"10.3390\/cells8010027"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3591","DOI":"10.1111\/febs.14393","article-title":"The role of glucocerebrosidase in Parkinson disease pathogenesis","volume":"285","author":"Gegg","year":"2018","journal-title":"FEBS J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.plipres.2015.09.002","article-title":"Control of inflammatory responses by ceramide, sphingosine 1-phosphate and ceramide 1-phosphate","volume":"61","author":"Presa","year":"2016","journal-title":"Prog. Lipid Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/978-3-030-21735-8_15","article-title":"Roles of Ceramides and Other Sphingolipids in Immune Cell Function and Inflammation","volume":"1161","author":"Albeituni","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1042\/EBC20190091","article-title":"Role of bioactive sphingolipids in physiology and pathology","volume":"64","author":"Presa","year":"2020","journal-title":"Essays Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.plipres.2010.02.004","article-title":"Control of metabolism and signaling of simple bioactive sphingolipids: Implications in disease","volume":"49","author":"Gangoiti","year":"2010","journal-title":"Prog. Lipid Res."},{"key":"ref_16","first-page":"433","article-title":"The Role of Lipids Interacting with \u03b1-Synuclein in the Pathogenesis of Parkinson\u2019s Disease","volume":"7","author":"Galvagnion","year":"2017","journal-title":"J. Park. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1002\/acn3.177","article-title":"Progressive decline of glucocerebrosidase in aging and P arkinson\u2019s disease","volume":"2","author":"Rocha","year":"2015","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"437","DOI":"10.3389\/fneur.2020.00437","article-title":"Exploring Sphingolipid Implications in Neurodegeneration","volume":"11","author":"Alessenko","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrm2329","article-title":"Principles of bioactive lipid signalling: Lessons from sphingolipids","volume":"9","author":"Hannun","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1002\/mds.27393","article-title":"Blood lysosphingolipids accumulation in patients with parkinson\u2019s disease with glucocerebrosidase 1 mutations","volume":"33","author":"Pchelina","year":"2018","journal-title":"Mov. Disord."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3389\/fnagi.2018.00051","article-title":"Promising Metabolite Profiles in the Plasma and CSF of Early Clinical Parkinson\u2019s Disease","volume":"10","author":"Stoessel","year":"2018","journal-title":"Front. Aging Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Custodia, A., Aramburu-N\u00fa\u00f1ez, M., Correa-Paz, C., Posado-Fern\u00e1ndez, A., G\u00f3mez-Larrauri, A., Castillo, J., G\u00f3mez-Mu\u00f1oz, A., Sobrino, T., and Ouro, A. (2021). Ceramide Metabolism and Parkinson\u2019s Disease\u2014Therapeutic Targets. Biomolecules, 11.","DOI":"10.3390\/biom11070945"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Mielke, M.M., Maetzler, W., Haughey, N.J., Bandaru, V.V.R., Savica, R., Deuschle, C., Gasser, T., Hauser, A.-K., Gr\u00e4ber-Sultan, S., and Schleicher, E. (2013). Plasma Ceramide and Glucosylceramide Metabolism Is Altered in Sporadic Parkinson\u2019s Disease and Associated with Cognitive Impairment: A Pilot Study. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0073094"},{"key":"ref_24","unstructured":"Franklin, K., and Paxinos, G. (2008). The Mouse Brain in Stereotaxic Coordinates, Compact, Academic Press. [3rd ed.]."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.nbd.2016.12.005","article-title":"Cooperative synthesis of dopamine by non-dopaminergic neurons as a compensatory mechanism in the striatum of mice with MPTP-induced Parkinsonism","volume":"98","author":"Kozina","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1139\/y59-099","article-title":"A rapid method of total lipid extraction and purification","volume":"37","author":"Bligh","year":"1959","journal-title":"Can. J. Biochem. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1134\/S1819712421020021","article-title":"Changes in the Content of Sphingolipids in the Nigrostriatal Dopaminergic System in the Brain of Mice with a Neurotoxic Model of Parkinson\u2019s Disease","volume":"15","author":"Alessenko","year":"2021","journal-title":"Neurochem. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.neuroscience.2011.03.007","article-title":"Modeling of presymptomatic and symptomatic stages of parkinsonism in mice","volume":"181","author":"Ugrumov","year":"2011","journal-title":"Neuroscience"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s00401-014-1284-0","article-title":"Cutaneous neuropathy in Parkinson\u2019s disease: A window into brain pathology","volume":"128","author":"Doppler","year":"2014","journal-title":"Acta Neuropathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.jns.2014.03.028","article-title":"Tyrosine hydroxylase expression and activity in nigrostriatal dopaminergic neurons of MPTP-treated mice at the presymptomatic and symptomatic stages of parkinsonism","volume":"340","author":"Kozina","year":"2014","journal-title":"J. Neurol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.1007\/s12035-017-0559-6","article-title":"MPTP Mouse Model of Preclinical and Clinical Parkinson\u2019s Disease as an Instrument for Translational Medicine","volume":"55","author":"Mingazov","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3437","DOI":"10.1007\/s12035-018-1315-2","article-title":"Upgraded Methodology for the Development of Early Diagnosis of Parkinson\u2019s Disease Based on Searching Blood Markers in Patients and Experimental Models","volume":"56","author":"Kim","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Bogdanov, V., Kim, A., Nodel, M., Pavlenko, T., Pavlova, E., Blokhin, V., Chesnokova, N., and Ugrumov, M. (2021). A Pilot Study of Changes in the Level of Catecholamines and the Activity of \u03b1-2-Macroglobulin in the Tear Fluid of Patients with Parkinson\u2019s Disease and Parkinsonian Mice. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094736"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1016\/0140-6736(91)92989-F","article-title":"Parkinson\u2019s disease: Pathophysiology","volume":"337","author":"Agid","year":"1991","journal-title":"Lancet"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"787","DOI":"10.3389\/fphys.2017.00787","article-title":"Brain Ceramide Metabolism in the Control of Energy Balance","volume":"8","author":"Campana","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1002\/mds.26278","article-title":"No evidence for substrate accumula-tion in Parkinson brains with GBA mutations","volume":"30","author":"Gegg","year":"2015","journal-title":"Mov. Disord."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1759091418781889","DOI":"10.1177\/1759091418781889","article-title":"Sex-Related Abnormalities in Substantia Nigra Lipids in Parkinson\u2019s Disease","volume":"10","author":"Seyfried","year":"2018","journal-title":"ASN Neuro"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1212\/WNL.0b013e31828f180e","article-title":"The p.L302P mutation in the lysosomal enzyme gene SMPD1 is a risk factor for Par-kinson disease","volume":"80","author":"Ozelius","year":"2013","journal-title":"Neurology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1001\/archneur.1969.00480180071006","article-title":"Sphingomyelin in Lewy Inclusion Bodies in Parkinson\u2019s Disease","volume":"21","year":"1969","journal-title":"Arch. Neurol."},{"key":"ref_40","first-page":"41","article-title":"Changes in Sphingomyelin Level Affect Alpha-Synuclein and ABCA5 Expression","volume":"2","author":"Kim","year":"2012","journal-title":"J. Park. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"9617","DOI":"10.1523\/JNEUROSCI.1525-17.2017","article-title":"Glucosylsphingosine Promotes \u03b1-Synuclein Pathology in Mutant GBA-Associated Parkinson\u2019s Disease","volume":"37","author":"Taguchi","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1007\/s12035-016-0317-1","article-title":"Alpha-synuclein alters differently gene expression of Sirts, PARPs and other stress response proteins: Implications for neurodegenerative disorders","volume":"55","author":"Motyl","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"260","DOI":"10.5114\/fn.2014.45567","article-title":"The key role of sphingosine kinases in the molecular mechanism of neuronal cell sur-vival and death in an experimental model of Parkinson\u2019s disease","volume":"52","author":"Pyszko","year":"2014","journal-title":"Folia Neuropathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1007\/s12035-013-8622-4","article-title":"Sphingosine Kinase 1 and Sphingosine-1-Phosphate in Oxidative Stress Evoked by 1-Methyl-4-Phenylpyridinium (MPP+) in Human Dopaminergic Neuronal Cells","volume":"50","author":"Pyszko","year":"2014","journal-title":"Mol. Neurobiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/j.neuroscience.2015.01.032","article-title":"Sphingosine kinase 2 and sphingosine-1-phosphate pro-motes mitochondrial function in dopaminergic neurons of mouse model of Parkinson\u2019s disease and in MPP+-treated MN9D cells in vitro","volume":"290","author":"Sivasubramanian","year":"2015","journal-title":"Neuroscience"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1096\/fj.201600751r","article-title":"Neuroprotective effects of fingolimod in mouse models of Parkinson\u2019s disease","volume":"31","author":"Zhao","year":"2017","journal-title":"FASEB J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1073\/pnas.1700465115","article-title":"GBA1 deficiency negatively affects physiological \u03b1-synuclein tetramers and related multimers","volume":"115","author":"Kim","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.neurobiolaging.2018.02.028","article-title":"Glycosphingolipid levels and glucocerebrosidase activity are altered in normal aging of the mouse brain","volume":"67","author":"Hallett","year":"2018","journal-title":"Neurobiol. Aging"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/S0079-6123(10)83001-8","article-title":"Identifying PD-causing genes and genetic susceptibility factors: Current approaches and future prospects","volume":"183","author":"Gasser","year":"2010","journal-title":"Prog. Brain Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3371","DOI":"10.1074\/jbc.X120.012838","article-title":"Sphingosine-1-phosphate: From insipid lipid to a key regulator","volume":"295","author":"Spiegel","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1016\/j.neurol.2021.01.015","article-title":"Mini review\u2014The role of Glucocerebrosidase and Progranulin as possible targets in the treatment of Parkinson\u2019s disease","volume":"177","author":"Rodrigues","year":"2021","journal-title":"Rev. Neurol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"105507","DOI":"10.1016\/j.nbd.2021.105507","article-title":"A novel glucosylceramide synthase inhibitor attenuates alpha synuclein pathology and lysosomal dysfunction in preclinical models of synucleinopathy","volume":"159","author":"Cosden","year":"2021","journal-title":"Neurobiol. 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