{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T09:40:46Z","timestamp":1792489246726,"version":"4.5.0"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No.82204357"],"award-info":[{"award-number":["No.82204357"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U25A20182"],"award-info":[{"award-number":["U25A20182"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20231267"],"award-info":[{"award-number":["BK20231267"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key R&D Program of China"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Neurosci"],"DOI":"10.1038\/s41593-026-02487-7","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T09:02:31Z","timestamp":1792486951000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dysregulated cholesterol trafficking through ABCA1 drives neurodegeneration in Parkinson\u2019s disease"],"prefix":"10.1038","author":[{"given":"Feng-xia","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-xin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-xin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo-yan","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shen-han","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-xiao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5813-9368","authenticated-orcid":false,"given":"Qiu-ling","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8018-8389","authenticated-orcid":false,"given":"Ming","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6493-1467","authenticated-orcid":false,"given":"Lei","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,20]]},"reference":[{"key":"2487_CR1","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/S0140-6736(23)01478-2","volume":"403","author":"HR Morris","year":"2024","unstructured":"Morris, H. R., Spillantini, M. G., Sue, C. M. & Williams-Gray, C. H. The pathogenesis of Parkinson\u2019s disease. Lancet 403, 293\u2013304 (2024).","journal-title":"Lancet"},{"key":"2487_CR2","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1056\/NEJMra2401857","volume":"391","author":"CM Tanner","year":"2024","unstructured":"Tanner, C. M. & Ostrem, J. L. Parkinson\u2019s disease. N. Engl. J. Med. 391, 442\u2013452 (2024).","journal-title":"N. Engl. J. Med."},{"key":"2487_CR3","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1016\/S1474-4422(21)00061-2","volume":"20","author":"N Vijiaratnam","year":"2021","unstructured":"Vijiaratnam, N., Simuni, T., Bandmann, O., Morris, H. R. & Foltynie, T. Progress towards therapies for disease modification in Parkinson\u2019s disease. Lancet Neurol. 20, 559\u2013572 (2021).","journal-title":"Lancet Neurol."},{"key":"2487_CR4","doi-asserted-by":"publisher","first-page":"899","DOI":"10.3233\/JPD-240272","volume":"14","author":"K McFarthing","year":"2024","unstructured":"McFarthing, K. et al. Parkinson\u2019s disease drug therapies in the clinical trial pipeline: 2024 update. J. Parkinsons Dis. 14, 899\u2013912 (2024).","journal-title":"J. Parkinsons Dis."},{"key":"2487_CR5","doi-asserted-by":"publisher","first-page":"554","DOI":"10.5607\/en.2019.28.5.554","volume":"28","author":"U Jin","year":"2019","unstructured":"Jin, U., Park, S. J. & Park, S. M. Cholesterol metabolism in the brain and its association with Parkinson\u2019s disease. Exp. Neurobiol. 28, 554\u2013567 (2019).","journal-title":"Exp. Neurobiol."},{"key":"2487_CR6","doi-asserted-by":"publisher","first-page":"e0171285","DOI":"10.1371\/journal.pone.0171285","volume":"12","author":"R Paul","year":"2017","unstructured":"Paul, R. et al. Cholesterol contributes to dopamine-neuronal loss in MPTP mouse model of Parkinson\u2019s disease: involvement of mitochondrial dysfunctions and oxidative stress. PLoS ONE 12, e0171285 (2017).","journal-title":"PLoS ONE"},{"key":"2487_CR7","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1159\/000481551","volume":"24","author":"A Raju","year":"2018","unstructured":"Raju, A., Jaisankar, P., Borah, A. & Mohanakumar, K. P. 1-Methyl-4-phenylpyridinium-induced death of differentiated SH-SY5Y neurons is potentiated by cholesterol. Ann. Neurosci. 24, 243\u2013251 (2018).","journal-title":"Ann. Neurosci."},{"key":"2487_CR8","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1161\/01.ATV.0000120374.59826.1b","volume":"24","author":"I Bjorkhem","year":"2004","unstructured":"Bjorkhem, I. & Meaney, S. Brain cholesterol: long secret life behind a barrier. Arterioscler. Thromb. Vasc. Biol. 24, 806\u2013815 (2004).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"2487_CR9","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1194\/jlr.R400004-JLR200","volume":"45","author":"JM Dietschy","year":"2004","unstructured":"Dietschy, J. M. & Turley, S. D. Thematic review series: brain lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal. J. Lipid Res. 45, 1375\u20131397 (2004).","journal-title":"J. Lipid Res."},{"key":"2487_CR10","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1001\/jamaneurol.2022.3718","volume":"79","author":"KN Stevens","year":"2022","unstructured":"Stevens, K. N. et al. Evaluation of simvastatin as a disease-modifying treatment for patients with Parkinson disease: a randomized clinical trial. JAMA Neurol. 79, 1232\u20131241 (2022).","journal-title":"JAMA Neurol."},{"key":"2487_CR11","doi-asserted-by":"publisher","first-page":"3191","DOI":"10.1093\/brain\/awab292","volume":"144","author":"SH Jeong","year":"2021","unstructured":"Jeong, S. H. et al. Effects of statins on dopamine loss and prognosis in Parkinson\u2019s disease. Brain 144, 3191\u20133200 (2021).","journal-title":"Brain"},{"key":"2487_CR12","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.tins.2022.01.002","volume":"45","author":"D Li","year":"2022","unstructured":"Li, D., Zhang, J. & Liu, Q. Brain cell type-specific cholesterol metabolism and implications for learning and memory. Trends Neurosci. 45, 401\u2013414 (2022).","journal-title":"Trends Neurosci."},{"key":"2487_CR13","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.ejcb.2017.01.002","volume":"96","author":"I Eriksson","year":"2017","unstructured":"Eriksson, I., Nath, S., Bornefall, P., Giraldo, A. M. & Ollinger, K. Impact of high cholesterol in a Parkinson\u2019s disease model: prevention of lysosomal leakage versus stimulation of \u03b1-synuclein aggregation. Eur. J. Cell Biol. 96, 99\u2013109 (2017).","journal-title":"Eur. J. Cell Biol."},{"key":"2487_CR14","doi-asserted-by":"publisher","first-page":"40987","DOI":"10.1074\/jbc.M407963200","volume":"279","author":"SE Wahrle","year":"2004","unstructured":"Wahrle, S. E. et al. ABCA1 is required for normal central nervous system ApoE levels and for lipidation of astrocyte-secreted apoE. J. Biol. Chem. 279, 40987\u201340993 (2004).","journal-title":"J. Biol. Chem."},{"key":"2487_CR15","doi-asserted-by":"publisher","first-page":"1786","DOI":"10.1038\/s41588-022-01208-7","volume":"54","author":"H Holstege","year":"2022","unstructured":"Holstege, H. et al. Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer\u2019s disease. Nat. Genet. 54, 1786\u20131794 (2022).","journal-title":"Nat. Genet."},{"key":"2487_CR16","doi-asserted-by":"publisher","first-page":"e2102191118","DOI":"10.1073\/pnas.2102191118","volume":"118","author":"H Wang","year":"2021","unstructured":"Wang, H. et al. Regulation of beta-amyloid production in neurons by astrocyte-derived cholesterol. Proc. Natl Acad. Sci. USA 118, e2102191118 (2021).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2487_CR17","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1038\/cdd.2014.162","volume":"22","author":"M Valenza","year":"2015","unstructured":"Valenza, M. et al. Disruption of astrocyte-neuron cholesterol cross talk affects neuronal function in Huntington\u2019s disease. Cell Death Differ. 22, 690\u2013702 (2015).","journal-title":"Cell Death Differ."},{"key":"2487_CR18","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1038\/s42255-023-00747-5","volume":"5","author":"K Roh","year":"2023","unstructured":"Roh, K. et al. Lysosomal control of senescence and inflammation through cholesterol partitioning. Nat. Metab. 5, 398\u2013413 (2023).","journal-title":"Nat. Metab."},{"key":"2487_CR19","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s13024-025-00802-7","volume":"20","author":"S Wang","year":"2025","unstructured":"Wang, S. et al. Cellular senescence induced by cholesterol accumulation is mediated by lysosomal ABCA1 in APOE4 and AD. Mol. Neurodegener. 20, 15 (2025).","journal-title":"Mol. Neurodegener."},{"key":"2487_CR20","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1038\/s41580-019-0190-7","volume":"21","author":"J Luo","year":"2020","unstructured":"Luo, J., Yang, H. & Song, B. L. Mechanisms and regulation of cholesterol homeostasis. Nat. Rev. Mol. Cell Biol. 21, 225\u2013245 (2020).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2487_CR21","doi-asserted-by":"publisher","first-page":"2142","DOI":"10.1038\/s42255-025-01365-z","volume":"7","author":"FM Feringa","year":"2025","unstructured":"Feringa, F. M. et al. The Neurolipid Atlas: a lipidomics resource for neurodegenerative diseases. Nat. Metab. 7, 2142\u20132164 (2025).","journal-title":"Nat. Metab."},{"key":"2487_CR22","doi-asserted-by":"publisher","first-page":"20","DOI":"10.31083\/j.jin2201020","volume":"22","author":"OC Ioghen","year":"2023","unstructured":"Ioghen, O. C., Ceafalan, L. C. & Popescu, B. O. SH-SY5Y cell line in vitro models for Parkinson disease research\u2014old practice for new trends. J. Integr. Neurosci. 22, 20 (2023).","journal-title":"J. Integr. Neurosci."},{"key":"2487_CR23","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adq2742","volume":"11","author":"Y Schneider","year":"2025","unstructured":"Schneider, Y. et al. Vimentin network dysregulation mediates neurite deficits in SNCA duplication Parkinson\u2019s patient-derived midbrain neurons. Sci. Adv. 11, eadq2742 (2025).","journal-title":"Sci. Adv."},{"key":"2487_CR24","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1038\/s41593-022-01061-1","volume":"25","author":"T Kamath","year":"2022","unstructured":"Kamath, T. et al. Single-cell genomic profiling of human dopamine neurons identifies a population that selectively degenerates in Parkinson\u2019s disease. Nat. Neurosci. 25, 588\u2013595 (2022).","journal-title":"Nat. Neurosci."},{"key":"2487_CR25","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1146\/annurev-physiol-031620-094944","volume":"83","author":"AM Plummer","year":"2021","unstructured":"Plummer, A. M., Culbertson, A. T. & Liao, M. The ABCs of sterol transport. Annu. Rev. Physiol. 83, 153\u2013181 (2021).","journal-title":"Annu. Rev. Physiol."},{"key":"2487_CR26","doi-asserted-by":"publisher","first-page":"eabc5062","DOI":"10.1126\/sciadv.abc5062","volume":"7","author":"L Cao","year":"2021","unstructured":"Cao, L. et al. Anti-Na+\/K+-ATPase immunotherapy ameliorates \u03b1-synuclein pathology through activation of Na+\/K+-ATPase \u03b11-dependent autophagy. Sci. Adv. 7, eabc5062 (2021).","journal-title":"Sci. Adv."},{"key":"2487_CR27","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.1126\/science.abg6621","volume":"377","author":"HR Shin","year":"2022","unstructured":"Shin, H. R. et al. Lysosomal GPCR-like protein LYCHOS signals cholesterol sufficiency to mTORC1. Science 377, 1290\u20131298 (2022).","journal-title":"Science"},{"key":"2487_CR28","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1007\/s12017-016-8435-5","volume":"19","author":"PS Guerreiro","year":"2017","unstructured":"Guerreiro, P. S. et al. Mutant A53T \u03b1-synuclein improves rotarod performance before motor deficits and affects metabolic pathways. Neuromolecular Med. 19, 113\u2013121 (2017).","journal-title":"Neuromolecular Med."},{"key":"2487_CR29","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s13024-024-00717-9","volume":"19","author":"A Martirosyan","year":"2024","unstructured":"Martirosyan, A. et al. Correction: unravelling cell type-specific responses to Parkinson\u2019s disease at single cell resolution. Mol. Neurodegener. 19, 28 (2024).","journal-title":"Mol. Neurodegener."},{"key":"2487_CR30","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.3233\/JPD-212670","volume":"11","author":"K Wang","year":"2021","unstructured":"Wang, K. et al. Blood cholesterol decreases as Parkinson\u2019s disease develops and progresses. J. Parkinsons Dis. 11, 1177\u20131186 (2021).","journal-title":"J. Parkinsons Dis."},{"key":"2487_CR31","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1159\/000323265","volume":"8","author":"K Ikeda","year":"2011","unstructured":"Ikeda, K. et al. Serological profiles of urate, paraoxonase-1, ferritin and lipid in Parkinson\u2019s disease: changes linked to disease progression. Neurodegener. Dis. 8, 252\u2013258 (2011).","journal-title":"Neurodegener. Dis."},{"key":"2487_CR32","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.1002\/mds.27413","volume":"33","author":"V Rozani","year":"2018","unstructured":"Rozani, V. et al. Higher serum cholesterol and decreased Parkinson\u2019s disease risk: a statin-free cohort study. Mov. Disord. 33, 1298\u20131305 (2018).","journal-title":"Mov. Disord."},{"key":"2487_CR33","doi-asserted-by":"publisher","first-page":"363","DOI":"10.3233\/JPD-130196","volume":"3","author":"K Gudala","year":"2013","unstructured":"Gudala, K., Bansal, D. & Muthyala, H. Role of serum cholesterol in Parkinson\u2019s disease: a meta-analysis of evidence. J. Parkinsons Dis. 3, 363\u2013370 (2013).","journal-title":"J. Parkinsons Dis."},{"key":"2487_CR34","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.phrs.2014.03.002","volume":"88","author":"CR Sirtori","year":"2014","unstructured":"Sirtori, C. R. The pharmacology of statins. Pharmacol. Res. 88, 3\u201311 (2014).","journal-title":"Pharmacol. Res."},{"key":"2487_CR35","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103190","volume":"73","author":"X Zhao","year":"2024","unstructured":"Zhao, X. et al. JWA binding to NCOA4 alleviates degeneration in dopaminergic neurons through suppression of ferritinophagy in Parkinson\u2019s disease. Redox Biol. 73, 103190 (2024).","journal-title":"Redox Biol."},{"key":"2487_CR36","doi-asserted-by":"publisher","first-page":"ENEURO.0327-21.","DOI":"10.1523\/ENEURO.0327-21.2022","volume":"9","author":"RT Clements","year":"2022","unstructured":"Clements, R. T. et al. Quantification of neurite degeneration with enhanced accuracy and efficiency in an in vitro model of Parkinson\u2019s disease. eNeuro 9, ENEURO.0327-21.2022 (2022).","journal-title":"eNeuro"},{"key":"2487_CR37","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-03442-1","volume":"11","author":"A Dravid","year":"2021","unstructured":"Dravid, A., Raos, B., Svirskis, D. & O\u2019Carroll, S. J. Optimised techniques for high-throughput screening of differentiated SH-SY5Y cells and application for neurite outgrowth assays. Sci. Rep. 11, 23935 (2021).","journal-title":"Sci. Rep."},{"key":"2487_CR38","doi-asserted-by":"publisher","first-page":"1746","DOI":"10.1002\/glia.24580","volume":"72","author":"LG Allende","year":"2024","unstructured":"Allende, L. G. et al. Lysosomal cholesterol accumulation in aged astrocytes impairs cholesterol delivery to neurons and can be rescued by cannabinoids. Glia 72, 1746\u20131765 (2024).","journal-title":"Glia"},{"key":"2487_CR39","doi-asserted-by":"publisher","first-page":"e61118","DOI":"10.3791\/61118","volume":"162","author":"S Er","year":"2020","unstructured":"Er, S., Hlushchuk, I., Airavaara, M., Chmielarz, P. & Domanskyi, A. Studying pre-formed fibril induced \u03b1-synuclein accumulation in primary embryonic mouse midbrain dopamine neurons. J. Vis. Exp. 162, e61118 https:\/\/doi.org\/10.3791\/61118 (2020).","journal-title":"J. Vis. Exp."}],"container-title":["Nature Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41593-026-02487-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41593-026-02487-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41593-026-02487-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T09:02:32Z","timestamp":1792486952000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41593-026-02487-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,20]]},"references-count":39,"alternative-id":["2487"],"URL":"https:\/\/doi.org\/10.1038\/s41593-026-02487-7","relation":{},"ISSN":["1097-6256","1546-1726"],"issn-type":[{"value":"1097-6256","type":"print"},{"value":"1546-1726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,20]]},"assertion":[{"value":"14 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 October 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","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}