{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:24:39Z","timestamp":1792790679725,"version":"4.5.0"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"vor","delay-in-days":26,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Korea Basic Science Institute (National research Facilities and Equipment Center) grant","award":["2023R1A6C101A045"],"award-info":[{"award-number":["2023R1A6C101A045"]}],"id":[{"id":"https:\/\/ror.org\/0417sdw47","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Bio & Medical Technology Development Program of the NRF","award":["RS-2024-00440824"],"award-info":[{"award-number":["RS-2024-00440824"]}]},{"name":"Korea Health Technology R&D Project through the Korea Health Industry Development Institute","award":["RS-2024-00439685"],"award-info":[{"award-number":["RS-2024-00439685"]}],"id":[{"id":"https:\/\/ror.org\/00fdzyk40","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Korean ARPA-H Project through the Korea Health Industry Development Institute","award":["RS-2024-00507256"],"award-info":[{"award-number":["RS-2024-00507256"]}],"id":[{"id":"https:\/\/ror.org\/00fdzyk40","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Research Council of Science & Technology (NST) grant","award":["CAP23021-000"],"award-info":[{"award-number":["CAP23021-000"]}],"id":[{"id":"https:\/\/ror.org\/058rymf81","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Parkinsons Dis."],"DOI":"10.1038\/s41531-026-01263-5","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:42:50Z","timestamp":1768956170000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Inhibition of de novo ceramide synthesis mitigates alpha-synuclein pathology in a Parkinson\u2019s disease mouse model"],"prefix":"10.1038","volume":"12","author":[{"given":"Eunkyung","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moon-young","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minkuk","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na-Yeong","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shibo","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahee","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongryeol","family":"Ryu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoon","family":"Ryu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dohyun","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gakyung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Myung","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"1263_CR1","doi-asserted-by":"crossref","unstructured":"Aarsland, D. et al. Parkinson disease-associated cognitive impairment. Nat. Rev. Dis. Primers 7, 47 (2021).","DOI":"10.1038\/s41572-021-00280-3"},{"key":"1263_CR2","doi-asserted-by":"crossref","unstructured":"Rocha, E. M., De Miranda, B. & Sanders, L. H. J. N. o. d. Alpha-synuclein: Pathology, mitochondrial dysfunction and neuroinflammation in Parkinson\u2019s disease. Neurobiol. Dis. 109, 249\u2013257 (2018).","DOI":"10.1016\/j.nbd.2017.04.004"},{"key":"1263_CR3","doi-asserted-by":"crossref","unstructured":"Iarkov, A., Barreto, G. E., Grizzell, J. A. & Echeverria, V. J. F. i. a. n. Strategies for the treatment of Parkinson\u2019s disease: beyond dopamine. Front. Aging Neurosci. 12, 4 (2020).","DOI":"10.3389\/fnagi.2020.00004"},{"key":"1263_CR4","doi-asserted-by":"crossref","unstructured":"Mitchell, C. L. & Kurouski, D. J. F. i. M. N. Novel strategies in Parkinson\u2019s disease treatment: a review. Front. Mol. Neurosci. 17, 1431079 (2024).","DOI":"10.3389\/fnmol.2024.1431079"},{"key":"1263_CR5","doi-asserted-by":"crossref","unstructured":"Young, M. M., Kester, M. & Wang, H.-G. J. J. o. l. r. Sphingolipids: regulators of crosstalk between apoptosis and autophagy. J. Lipid Res. 54, 5\u201319 (2013).","DOI":"10.1194\/jlr.R031278"},{"key":"1263_CR6","doi-asserted-by":"publisher","first-page":"1597","DOI":"10.1038\/s42003-024-07231-0","volume":"7","author":"JJ McInnis","year":"2024","unstructured":"McInnis, J. J. et al. Unravelling neuronal and glial differences in ceramide composition, synthesis, and sensitivity to toxicity. Commun. Biol. 7, 1597 (2024).","journal-title":"Commun. Biol."},{"key":"1263_CR7","doi-asserted-by":"crossref","unstructured":"Jana, A., Hogan, E. L. & Pahan, K. J. J. o. t. n. s. Ceramide and neurodegeneration: susceptibility of neurons and oligodendrocytes to cell damage and death. J. Neurol. Sci. 278, 5\u201315 (2009).","DOI":"10.1016\/j.jns.2008.12.010"},{"key":"1263_CR8","doi-asserted-by":"publisher","first-page":"6469","DOI":"10.3390\/ijms22126469","volume":"22","author":"A Mingione","year":"2021","unstructured":"Mingione, A. et al. Inhibition of ceramide synthesis reduces \u03b1-synuclein proteinopathy in a cellular model of Parkinson\u2019s disease. Int. J. Mol. Sci. 22, 6469 (2021).","journal-title":"Int. J. Mol. Sci."},{"key":"1263_CR9","doi-asserted-by":"crossref","unstructured":"Lim, J. R. et al. Ethanol-induced ceramide production causes neuronal apoptosis by increasing MCL-1S-mediated ER-mitochondria contacts. Neurobiol. Dis. 177, 106009 (2023).","DOI":"10.1016\/j.nbd.2023.106009"},{"key":"1263_CR10","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.ade6509","volume":"15","author":"TI Lima","year":"2023","unstructured":"Lima, T. I. et al. Inhibiting de novo ceramide synthesis restores mitochondrial and protein homeostasis in muscle aging. Sci. Transl. Med. 15, eade6509 (2023).","journal-title":"Sci. Transl. Med."},{"key":"1263_CR11","doi-asserted-by":"crossref","unstructured":"Poisson, J. et al. Safe and orally bioavailable inhibitor of serine palmitoyltransferase improves age-related sarcopenia. ACS Pharmacol. Transl. Sci. 8, 203\u2013215 (2024).","DOI":"10.1021\/acsptsci.4c00587"},{"key":"1263_CR12","doi-asserted-by":"crossref","unstructured":"Kon, T., Tomiyama, M. & Wakabayashi, K. J. N. Neuropathology of Lewy body disease: clinicopathological crosstalk between typical and atypical cases. Neuropathology 40, 30\u201339 (2020).","DOI":"10.1111\/neup.12597"},{"key":"1263_CR13","doi-asserted-by":"crossref","unstructured":"Kok, M.-Y. A. & Fu, Y. J. J. o. N. M. A new mouse tool for studying dopaminergic neurons. J. Neurosci. Methods 347, 108968 (2021).","DOI":"10.1016\/j.jneumeth.2020.108968"},{"key":"1263_CR14","doi-asserted-by":"crossref","unstructured":"Nayak, S. U. et al. Chemokine CCR5 and cocaine interactions in the brain: Cocaine enhances mesolimbic CCR5 mRNA levels and produces place preference and locomotor activation that are reduced by a CCR5 antagonist. Brain Behav. Immun. 83, 288\u2013292 (2020).","DOI":"10.1016\/j.bbi.2019.09.017"},{"key":"1263_CR15","doi-asserted-by":"crossref","unstructured":"Zhou, P., Xu, P., Yu, W., Li, H. J. J., O. O. S. & Research. MiR-206 improves intervertebral disk degeneration by targeting GJA1. J. Orthop. Surg. Res. 17, 157 (2022).","DOI":"10.1186\/s13018-022-03044-1"},{"key":"1263_CR16","doi-asserted-by":"crossref","unstructured":"Yang, S. et al. AZGP1 aggravates macrophage M1 polarization and pyroptosis in periodontitis. J. Dent. Res. 103, 631\u2013641 (2024).","DOI":"10.1177\/00220345241235616"},{"key":"1263_CR17","doi-asserted-by":"publisher","unstructured":"Kearney, P. J. et al. Rit2 silencing in dopamine neurons drives a Parkinsonian phenotype. Preprint https:\/\/doi.org\/10.1101\/2023.04.26.538430 (2023).","DOI":"10.1101\/2023.04.26.538430"},{"key":"1263_CR18","doi-asserted-by":"crossref","unstructured":"Plotegher, N., Bubacco, L., Greggio, E. & Civiero, L. J. F. i. N. Ceramides in Parkinson\u2019s disease: from recent evidence to new hypotheses. Front. Neurosci. 13, 330 (2019).","DOI":"10.3389\/fnins.2019.00330"},{"key":"1263_CR19","first-page":"2020","volume":"9","author":"S Aoki","year":"2022","unstructured":"Aoki, S., Funakoshi, T., Aki, T. & Uemura, K. J. T. r. Aggregation-prone A53T mutant of \u03b1-synuclein exaggerates methamphetamine neurotoxicity in SH-SY5Y. Cells. Prot. Role Cell. Cholest. 9, 2020\u20132029 (2022).","journal-title":"Cells. Prot. Role Cell. Cholest."},{"key":"1263_CR20","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.591475","volume":"13","author":"A Wilkaniec","year":"2021","unstructured":"Wilkaniec, A. et al. Exogenous alpha-synuclein evoked parkin downregulation promotes mitochondrial dysfunction in neuronal cells. implications for Parkinson\u2019s disease pathology. Front. Aging Neurosci. 13, 591475 (2021).","journal-title":"Front. Aging Neurosci."},{"key":"1263_CR21","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/S0896-6273(02)00682-7","volume":"34","author":"BI Giasson","year":"2002","unstructured":"Giasson, B. I. et al. Neuronal \u03b1-synucleinopathy with severe movement disorder in mice expressing A53T human \u03b1-synuclein. Neuron 34, 521\u2013533 (2002).","journal-title":"Neuron"},{"key":"1263_CR22","doi-asserted-by":"crossref","unstructured":"Minakaki, G., Krainc, D., Burbulla, L. F. J. F. i. C. & Biology, D. The convergence of alpha-synuclein, mitochondrial, and lysosomal pathways in vulnerability of midbrain dopaminergic neurons in Parkinson\u2019s disease. Front. Cell Dev. Biol. 8, 580634 (2020).","DOI":"10.3389\/fcell.2020.580634"},{"key":"1263_CR23","doi-asserted-by":"crossref","unstructured":"Biber, K. & Boddeke, E. J. F. i. c. n. Neuronal CC chemokines: the distinct roles of CCL21 and CCL2 in neuropathic pain. Front. Cell Neurosci. 8, 210 (2014).","DOI":"10.3389\/fncel.2014.00210"},{"key":"1263_CR24","doi-asserted-by":"crossref","unstructured":"Lee, H.-j. et al. Regulation of habenular G-protein gamma 8 on learning and memory via modulation of the central acetylcholine system. Mol. Psychiatry 26, 3737\u20133750 (2021).","DOI":"10.1038\/s41380-020-00893-2"},{"key":"1263_CR25","doi-asserted-by":"crossref","unstructured":"Marzinke, M. A. et al. Calmin expression in embryos and the adult brain, and its regulation by all-trans retinoic acid. Dev. Dyn. 239, 610\u2013619 (2010).","DOI":"10.1002\/dvdy.22171"},{"key":"1263_CR26","doi-asserted-by":"crossref","unstructured":"Spielman, L. et al. Induction of the complement component C1qB in brain of transgenic mice with neuronal overexpression of human cyclooxygenase-2. Acta Neuropathol. 103, 157\u2013162 (2002).","DOI":"10.1007\/s004010100447"},{"key":"1263_CR27","doi-asserted-by":"crossref","unstructured":"Halim, D. O., Munson, M. & Gao, F.-B. J. H. G. The exocyst complex in neurological disorders. Hum. Genet. 142, 1263\u20131270 (2023).","DOI":"10.1007\/s00439-023-02558-w"},{"key":"1263_CR28","doi-asserted-by":"crossref","unstructured":"Sun, N. et al. A fluorescence-based imaging method to measure in vitro and in vivo mitophagy using mt-Keima. Nat. Protoc. 12, 1576-1587 (2017).","DOI":"10.1038\/nprot.2017.060"},{"key":"1263_CR29","doi-asserted-by":"crossref","unstructured":"Wang, S., Jin, Z., Wu, B., Morris, A. J. & Deng, P. J. J. o. L. R. Role of dietary and nutritional interventions in ceramide-associated diseases. J. Lipid Res. 66, 100726 (2024).","DOI":"10.1016\/j.jlr.2024.100726"},{"key":"1263_CR30","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1007\/s00018-012-1038-x","volume":"70","author":"C Mencarelli","year":"2013","unstructured":"Mencarelli, C. & Martinez\u2013Martinez, P. Ceramide function in the brain: when a slight tilt is enough. Cell. Mol. Life Sci. 70, 181\u2013203 (2013).","journal-title":"Cell. Mol. Life Sci."},{"key":"1263_CR31","unstructured":"Riebeling, C. & Futerman, A. H. in Madame Curie Bioscience Database (Landes Bioscience, 2013)."},{"key":"1263_CR32","doi-asserted-by":"crossref","unstructured":"Schenck, M. et al. Ceramide: physiological and pathophysiological aspects. Arch. Biochem. Biophys. 462, 171\u2013175 (2007).","DOI":"10.1016\/j.abb.2007.03.031"},{"key":"1263_CR33","doi-asserted-by":"publisher","first-page":"2606","DOI":"10.1074\/jbc.M409066200","volume":"280","author":"KP Becker","year":"2005","unstructured":"Becker, K. P., Kitatani, K., Idkowiak-Baldys, J., Bielawski, J. & Hannun, Y. A. Selective inhibition of juxtanuclear translocation of protein kinase C \u03b2II by a negative feedback mechanism involving ceramide formed from the salvage pathway. J. Biol. Chem. 280, 2606\u20132612 (2005).","journal-title":"J. Biol. Chem."},{"key":"1263_CR34","doi-asserted-by":"crossref","unstructured":"Poewe, W. et al. Parkinson disease. Nat. Rev. Dis. Primers 3, 17013 (2017).","DOI":"10.1038\/nrdp.2017.13"},{"key":"1263_CR35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.brainres.2010.04.061","volume":"1343","author":"S Phani","year":"2010","unstructured":"Phani, S., Gonye, G. & Iacovitti, L. VTA neurons show a potentially protective transcriptional response to MPTP. Brain Res. 1343, 1\u201313 (2010).","journal-title":"Brain Res."},{"key":"1263_CR36","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1016\/j.nbd.2006.04.007","volume":"23","author":"M Maingay","year":"2006","unstructured":"Maingay, M., Romero-Ramos, M., Carta, M. & Kirik, D. Ventral tegmental area dopamine neurons are resistant to human mutant alpha-synuclein overexpression. Neurobiol. Dis. 23, 522\u2013532 (2006).","journal-title":"Neurobiol. Dis."},{"key":"1263_CR37","first-page":"1508","volume":"16","author":"JS Yu","year":"2024","unstructured":"Yu, J. S. et al. Lipidomic assessment of the inhibitory effect of standardized water extract of Hydrangea serrata (Thunb.) Ser. Leaves Adipogenes. 16, 1508 (2024).","journal-title":"Leaves Adipogenes."},{"key":"1263_CR38","doi-asserted-by":"publisher","first-page":"48562","DOI":"10.1074\/jbc.M406649200","volume":"279","author":"NL Alderson","year":"2004","unstructured":"Alderson, N. L. et al. The human FA2H gene encodes a fatty acid 2-hydroxylase. J. Biol. Chem. 279, 48562\u201348568 (2004).","journal-title":"J. Biol. Chem."},{"key":"1263_CR39","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39274-y","volume":"14","author":"T Xie","year":"2023","unstructured":"Xie, T. et al. Ceramide sensing by human SPT-ORMDL complex for establishing sphingolipid homeostasis. Nat. Commun. 14, 3475 (2023).","journal-title":"Nat. Commun."},{"key":"1263_CR40","doi-asserted-by":"publisher","first-page":"945","DOI":"10.3390\/biom11070945","volume":"11","author":"A Custodia","year":"2021","unstructured":"Custodia, A. et al. Ceramide metabolism and Parkinson\u2019s disease\u2014therapeutic targets. Biomolecules 11, 945 (2021).","journal-title":"Biomolecules"},{"key":"1263_CR41","doi-asserted-by":"publisher","first-page":"101236","DOI":"10.1016\/j.plipres.2023.101236","volume":"91","author":"F-Y Tzou","year":"2023","unstructured":"Tzou, F.-Y., Hornemann, T., Yeh, J.-Y. & Huang, S.-Y. The pathophysiological role of dihydroceramide desaturase in the nervous system. Prog. Lipid Res. 91, 101236 (2023).","journal-title":"Prog. Lipid Res."},{"key":"1263_CR42","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1002\/iub.319","volume":"62","author":"M Levy","year":"2010","unstructured":"Levy, M. & Futerman, A. H. Mammalian ceramide synthases. IUBMB Life 62, 347\u2013356 (2010).","journal-title":"IUBMB Life"},{"key":"1263_CR43","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2021.100628","volume":"2","author":"M Rai","year":"2021","unstructured":"Rai, M. et al. Analysis of proteostasis during aging with western blot of detergent-soluble and insoluble protein fractions. STAR Protoc. 2, 100628 (2021).","journal-title":"STAR Protoc."},{"key":"1263_CR44","doi-asserted-by":"publisher","first-page":"e23939","DOI":"10.1371\/journal.pone.0023939","volume":"6","author":"BR Lee","year":"2011","unstructured":"Lee, B. R. & Kamitani, T. Improved immunodetection of endogenous \u03b1-synuclein. PloS ONE 6, e23939 (2011).","journal-title":"PloS ONE"},{"key":"1263_CR45","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abh4423","volume":"8","author":"P-P Laurila","year":"2022","unstructured":"Laurila, P.-P. et al. Inhibition of sphingolipid de novo synthesis counteracts muscular dystrophy. Sci. Adv. 8, eabh4423 (2022).","journal-title":"Sci. Adv."}],"container-title":["npj Parkinson's Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41531-026-01263-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41531-026-01263-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41531-026-01263-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T17:03:48Z","timestamp":1771434228000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41531-026-01263-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,21]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1263"],"URL":"https:\/\/doi.org\/10.1038\/s41531-026-01263-5","relation":{},"ISSN":["2373-8057"],"issn-type":[{"value":"2373-8057","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,21]]},"assertion":[{"value":"22 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"49"}}