{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T17:13:35Z","timestamp":1771607615063,"version":"3.50.1"},"reference-count":75,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Science and Technology Program of the Joint Fund of Scientific Research for the Public Hospitals of Inner Mongolia Academy of Medical Sciences","award":["2023090101, 2024GLLH0988"],"award-info":[{"award-number":["2023090101, 2024GLLH0988"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NO.82471259"],"award-info":[{"award-number":["NO.82471259"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005046","name":"Heilongjiang Provincial Natural Science Foundation","doi-asserted-by":"crossref","award":["NO. ZD2023H004"],"award-info":[{"award-number":["NO. ZD2023H004"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-11481-1","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T16:25:09Z","timestamp":1752596709000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploring the mechanism of metabolic cell death-related genes AKR1C2 and MAP1LC3A as biomarkers in Parkinson\u2019s disease"],"prefix":"10.1038","volume":"15","author":[{"given":"Jia","family":"Fu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Mi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueying","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lige","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yali","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8809-6523","authenticated-orcid":false,"given":"Lifen","family":"Yao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,7,15]]},"reference":[{"key":"11481_CR1","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/s1474-4422(21)00030-2","volume":"20","author":"E Tolosa","year":"2021","unstructured":"Tolosa, E., Garrido, A., Scholz, S. W. & Poewe, W. Challenges in the diagnosis of parkinson\u2019s disease. Lancet Neurol. 20, 385\u2013397. https:\/\/doi.org\/10.1016\/s1474-4422(21)00030-2 (2021).","journal-title":"Lancet Neurol."},{"key":"11481_CR2","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1007\/s40265-022-01747-7","volume":"82","author":"DG Di Luca","year":"2022","unstructured":"Di Luca, D. G., Reyes, N. G. D. & Fox, S. H. Newly approved and investigational drugs for motor symptom control in parkinson\u2019s disease. Drugs. 82, 1027\u20131053. https:\/\/doi.org\/10.1007\/s40265-022-01747-7 (2022).","journal-title":"Drugs"},{"key":"11481_CR3","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1038\/s41577-022-00684-6","volume":"22","author":"MG Tansey","year":"2022","unstructured":"Tansey, M. G. et al. Inflammation and immune dysfunction in Parkinson disease. Nat. Rev. Immunol. 22, 657\u2013673. https:\/\/doi.org\/10.1038\/s41577-022-00684-6 (2022).","journal-title":"Nat. Rev. Immunol."},{"key":"11481_CR4","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1093\/procel\/pwae003","volume":"15","author":"C Mao","year":"2024","unstructured":"Mao, C., Wang, M., Zhuang, L. & Gan, B. Metabolic cell death in cancer: ferroptosis, cuproptosis, disulfidptosis, and beyond. Protein Cell. 15, 642\u2013660. https:\/\/doi.org\/10.1093\/procel\/pwae003 (2024).","journal-title":"Protein Cell."},{"key":"11481_CR5","doi-asserted-by":"publisher","unstructured":"Guo, D., Liu, Z., Zhou, J., Ke, C. & Li, D. Significance of programmed cell death pathways in neurodegenerative diseases. Int. J. Mol. Sci. 25 https:\/\/doi.org\/10.3390\/ijms25189947 (2024).","DOI":"10.3390\/ijms25189947"},{"key":"11481_CR6","doi-asserted-by":"publisher","unstructured":"Ding, X. S. et al. Ferroptosis in Parkinson\u2019s disease: Molecular mechanisms and therapeutic potential. Ageing Res. Rev. 91 https:\/\/doi.org\/10.1016\/j.arr.2023.102077 (2023).","DOI":"10.1016\/j.arr.2023.102077"},{"key":"11481_CR7","doi-asserted-by":"publisher","unstructured":"Lin, K. J. et al. Iron brain menace: the involvement of ferroptosis in Parkinson disease. Cells. 11 https:\/\/doi.org\/10.3390\/cells11233829 (2022).","DOI":"10.3390\/cells11233829"},{"key":"11481_CR8","doi-asserted-by":"publisher","first-page":"884748","DOI":"10.3389\/fcell.2022.884748","volume":"10","author":"R Cuevas-Diaz Duran","year":"2022","unstructured":"Cuevas-Diaz Duran, R., Gonz\u00e1lez-Orozco, J. C., Velasco, I. & Wu, J. Q. Single-cell and single-nuclei RNA sequencing as powerful tools to Decipher cellular heterogeneity and dysregulation in neurodegenerative diseases. Front. Cell. Dev. Biol. 10, 884748. https:\/\/doi.org\/10.3389\/fcell.2022.884748 (2022).","journal-title":"Front. Cell. Dev. Biol."},{"key":"11481_CR9","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1186\/s13046-021-01874-1","volume":"40","author":"Y Zhang","year":"2021","unstructured":"Zhang, Y. et al. Single-cell RNA sequencing in cancer research. J. Exp. Clin. Cancer Res. CR. 40, 81. https:\/\/doi.org\/10.1186\/s13046-021-01874-1 (2021).","journal-title":"J. Exp. Clin. Cancer Res. CR"},{"key":"11481_CR10","doi-asserted-by":"publisher","unstructured":"Ma, S. X. & Lim, S. B. Single-cell RNA sequencing in Parkinson\u2019s disease. Biomedicines. 9 https:\/\/doi.org\/10.3390\/biomedicines9040368 (2021).","DOI":"10.3390\/biomedicines9040368"},{"key":"11481_CR11","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/s41531-024-00790-3","volume":"10","author":"LL Xiong","year":"2024","unstructured":"Xiong, L. L. et al. Single-cell RNA sequencing reveals peripheral immunological features in Parkinson\u2019s disease. NPJ Parkinson\u2019s Dis.. 10, 185. https:\/\/doi.org\/10.1038\/s41531-024-00790-3 (2024).","journal-title":"NPJ Parkinson\u2019s Dis."},{"key":"11481_CR12","doi-asserted-by":"publisher","first-page":"lqaa077","DOI":"10.1093\/nargab\/lqaa077","volume":"2","author":"Z Hu","year":"2020","unstructured":"Hu, Z., Zu, S. & Liu, J. S. SIMPLEs: a single-cell RNA sequencing imputation strategy preserving gene modules and cell clusters variation. NAR Genom. Bioinf. 2, lqaa077. https:\/\/doi.org\/10.1093\/nargab\/lqaa077 (2020).","journal-title":"NAR Genom. Bioinf."},{"key":"11481_CR13","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1016\/j.stem.2020.11.015","volume":"28","author":"AM Ranzoni","year":"2021","unstructured":"Ranzoni, A. M. et al. Integrative Single-Cell RNA-Seq and ATAC-Seq analysis of human developmental hematopoiesis. Cell. Stem Cell. 28, 472\u2013487e477. https:\/\/doi.org\/10.1016\/j.stem.2020.11.015 (2021).","journal-title":"Cell. Stem Cell."},{"key":"11481_CR14","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1038\/s41467-023-36635-5","volume":"14","author":"X Yu","year":"2023","unstructured":"Yu, X., Xu, X., Zhang, J. & Li, X. Batch alignment of single-cell transcriptomics data using deep metric learning. Nat. Commun. 14, 960. https:\/\/doi.org\/10.1038\/s41467-023-36635-5 (2023).","journal-title":"Nat. Commun."},{"key":"11481_CR15","doi-asserted-by":"publisher","unstructured":"Lesnick, T. G. et al. A genomic pathway approach to a complex disease: axon guidance and Parkinson disease. PLoS Genet. 3, e98. https:\/\/doi.org\/10.1371\/journal.pgen.0030098 (2007).","DOI":"10.1371\/journal.pgen.0030098"},{"key":"11481_CR16","doi-asserted-by":"publisher","first-page":"e0128651","DOI":"10.1371\/journal.pone.0128651","volume":"10","author":"AA Dijkstra","year":"2015","unstructured":"Dijkstra, A. A. et al. Evidence for immune response, axonal dysfunction and reduced endocytosis in the substantia Nigra in early stage parkinson\u2019s disease. PLoS One. 10, e0128651. https:\/\/doi.org\/10.1371\/journal.pone.0128651 (2015).","journal-title":"PLoS One"},{"key":"11481_CR17","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1093\/brain\/awab446","volume":"145","author":"S Smaji\u0107","year":"2022","unstructured":"Smaji\u0107, S. et al. Single-cell sequencing of human midbrain reveals glial activation and a Parkinson-specific neuronal state. Brain J. Neurol. 145, 964\u2013978. https:\/\/doi.org\/10.1093\/brain\/awab446 (2022).","journal-title":"Brain J. Neurol."},{"key":"11481_CR18","doi-asserted-by":"publisher","unstructured":"Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Research 43, e47. https:\/\/doi.org\/10.1093\/nar\/gkv007 (2015).","DOI":"10.1093\/nar\/gkv007"},{"key":"11481_CR19","doi-asserted-by":"publisher","first-page":"3844","DOI":"10.1093\/bioinformatics\/btac409","volume":"38","author":"EK Gustavsson","year":"2022","unstructured":"Gustavsson, E. K., Zhang, D., Reynolds, R. H., Garcia-Ruiz, S. & Ryten, M. Ggtranscript: an R package for the visualization and interpretation of transcript isoforms using ggplot2. Bioinf. (Oxford England). 38, 3844\u20133846. https:\/\/doi.org\/10.1093\/bioinformatics\/btac409 (2022).","journal-title":"Bioinf. (Oxford England)"},{"key":"11481_CR20","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1093\/bioinformatics\/btab806","volume":"38","author":"Z Gu","year":"2022","unstructured":"Gu, Z. & H\u00fcbschmann, D. Make interactive complex heatmaps. Bioinf. (Oxford England). 38, 1460\u20131462. https:\/\/doi.org\/10.1093\/bioinformatics\/btab806 (2022).","journal-title":"Bioinf. (Oxford England)"},{"key":"11481_CR21","doi-asserted-by":"publisher","first-page":"906753","DOI":"10.3389\/fcvm.2022.906753","volume":"9","author":"Y Zheng","year":"2022","unstructured":"Zheng, Y. et al. Ferroptosis and autophagy-related genes in the pathogenesis of ischemic cardiomyopathy. Front. Cardiovasc. Med. 9, 906753. https:\/\/doi.org\/10.3389\/fcvm.2022.906753 (2022).","journal-title":"Front. Cardiovasc. Med."},{"key":"11481_CR22","doi-asserted-by":"publisher","first-page":"D672","DOI":"10.1093\/nar\/gkae909","volume":"53","author":"M Kanehisa","year":"2025","unstructured":"Kanehisa, M., Furumichi, M., Sato, Y., Matsuura, Y. & Ishiguro-Watanabe, M. KEGG: biological systems database as a model of the real world. Nucleic Acids Res. 53, D672\u2013d677. https:\/\/doi.org\/10.1093\/nar\/gkae909 (2025).","journal-title":"Nucleic Acids Res."},{"key":"11481_CR23","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa, M. & Goto, S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28, 27\u201330. https:\/\/doi.org\/10.1093\/nar\/28.1.27 (2000).","journal-title":"Nucleic Acids Res."},{"key":"11481_CR24","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1002\/pro.3715","volume":"28","author":"M Kanehisa","year":"2019","unstructured":"Kanehisa, M. Toward Understanding the origin and evolution of cellular organisms. Protein Sci. Publ. Protein Soc. 28, 1947\u20131951. https:\/\/doi.org\/10.1002\/pro.3715 (2019).","journal-title":"Protein Sci. Publ. Protein Soc."},{"key":"11481_CR25","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","volume":"16","author":"G Yu","year":"2012","unstructured":"Yu, G., Wang, L. G., Han, Y. & He, Q. Y. ClusterProfiler: an R package for comparing biological themes among gene clusters. Omics J. Integr. Biol. 16, 284\u2013287. https:\/\/doi.org\/10.1089\/omi.2011.0118 (2012).","journal-title":"Omics J. Integr. Biol."},{"key":"11481_CR26","doi-asserted-by":"publisher","first-page":"11340","DOI":"10.1038\/s41598-022-15609-5","volume":"12","author":"Y Li","year":"2022","unstructured":"Li, Y., Lu, F. & Yin, Y. Applying logistic LASSO regression for the diagnosis of atypical crohn\u2019s disease. Sci. Rep. 12, 11340. https:\/\/doi.org\/10.1038\/s41598-022-15609-5 (2022).","journal-title":"Sci. Rep."},{"key":"11481_CR27","doi-asserted-by":"publisher","first-page":"152","DOI":"10.21037\/atm.2019.03.29","volume":"7","author":"Z Zhang","year":"2019","unstructured":"Zhang, Z., Zhao, Y., Canes, A., Steinberg, D. & Lyashevska, O. Predictive analytics with gradient boosting in clinical medicine. Ann. Transl. Med. 7, 152. https:\/\/doi.org\/10.21037\/atm.2019.03.29 (2019).","journal-title":"Ann. Transl. Med."},{"key":"11481_CR28","doi-asserted-by":"publisher","unstructured":"Sachs, M. C. & plotROC: A tool for plotting ROC curves. J. Stat. Softw. 79 https:\/\/doi.org\/10.18637\/jss.v079.c02 (2017).","DOI":"10.18637\/jss.v079.c02"},{"key":"11481_CR29","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/1471-2105-12-77","volume":"12","author":"X Robin","year":"2011","unstructured":"Robin, X. et al. pROC: an open-source package for R and S\u2009+\u2009to analyze and compare ROC curves. BMC Bioinform. 12, 77. https:\/\/doi.org\/10.1186\/1471-2105-12-77 (2011).","journal-title":"BMC Bioinform."},{"key":"11481_CR30","doi-asserted-by":"publisher","unstructured":"Correction to Lancet Psych 2022; 9: 938. Lancet. Psychiatry 10, e10. https:\/\/doi.org\/10.1016\/s2215-0366(22)00411-4 (2023).","DOI":"10.1016\/s2215-0366(22)00411-4"},{"key":"11481_CR31","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1007\/978-1-4939-7493-1_12","volume":"1711","author":"B Chen","year":"2018","unstructured":"Chen, B., Khodadoust, M. S., Liu, C. L., Newman, A. M. & Alizadeh, A. A. Profiling tumor infiltrating immune cells with CIBERSORT. Methods Mol. Biol. (Clifton N J). 1711, 243\u2013259. https:\/\/doi.org\/10.1007\/978-1-4939-7493-1_12 (2018).","journal-title":"Methods Mol. Biol. (Clifton N J)"},{"key":"11481_CR32","doi-asserted-by":"publisher","unstructured":"Zeng, D. et al. Multi-Omics Immuno-Oncology biological research to Decode tumor microenvironment and signatures. Front. Immunol. 12 https:\/\/doi.org\/10.3389\/fimmu.2021.687975 (2021).","DOI":"10.3389\/fimmu.2021.687975"},{"key":"11481_CR33","doi-asserted-by":"publisher","unstructured":"Liu, P., Xu, H., Shi, Y., Deng, L. & Chen, X. Potential molecular mechanisms of plantain in the treatment of gout and hyperuricemia based on network Pharmacology. Evid.-Based Complement. Altern. Med. eCAM. 2020 (3023127). https:\/\/doi.org\/10.1155\/2020\/3023127 (2020).","DOI":"10.1155\/2020\/3023127"},{"key":"11481_CR34","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/nbt.3192","volume":"33","author":"R Satija","year":"2015","unstructured":"Satija, R., Farrell, J. A., Gennert, D., Schier, A. F. & Regev, A. Spatial reconstruction of single-cell gene expression data. Nat. Biotechnol. 33, 495\u2013502. https:\/\/doi.org\/10.1038\/nbt.3192 (2015).","journal-title":"Nat. Biotechnol."},{"key":"11481_CR35","doi-asserted-by":"publisher","first-page":"919731","DOI":"10.3389\/fcell.2022.919731","volume":"10","author":"Z Fang","year":"2022","unstructured":"Fang, Z. et al. Single-cell transcriptomics of proliferative phase endometrium: systems analysis of cell-cell communication network using cellchat. Front. Cell. Dev. Biol. 10, 919731. https:\/\/doi.org\/10.3389\/fcell.2022.919731 (2022).","journal-title":"Front. Cell. Dev. Biology"},{"key":"11481_CR36","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1038\/s41586-019-0969-x","volume":"566","author":"J Cao","year":"2019","unstructured":"Cao, J. et al. The single-cell transcriptional landscape of mammalian organogenesis. Nature. 566, 496\u2013502. https:\/\/doi.org\/10.1038\/s41586-019-0969-x (2019).","journal-title":"Nature"},{"key":"11481_CR37","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/nprot.2006.342","volume":"2","author":"V Jackson-Lewis","year":"2007","unstructured":"Jackson-Lewis, V. & Przedborski, S. Protocol for the MPTP mouse model of Parkinson\u2019s disease. Nat. Protoc. 2, 141\u2013151. https:\/\/doi.org\/10.1038\/nprot.2006.342 (2007).","journal-title":"Nat. Protoc."},{"key":"11481_CR38","doi-asserted-by":"publisher","unstructured":"Zhao, H. et al. Identification ferroptosis-related hub genes and diagnostic model in Alzheimer\u2019s disease. Front. Mol. Neurosci. 16 https:\/\/doi.org\/10.3389\/fnmol.2023.1280639 (2023).","DOI":"10.3389\/fnmol.2023.1280639"},{"key":"11481_CR39","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1038\/s41422-020-00441-1","volume":"31","author":"D Tang","year":"2021","unstructured":"Tang, D., Chen, X., Kang, R. & Kroemer, G. Ferroptosis: molecular mechanisms and health implications. Cell Res. 31, 107\u2013125. https:\/\/doi.org\/10.1038\/s41422-020-00441-1 (2021).","journal-title":"Cell Res."},{"key":"11481_CR40","doi-asserted-by":"publisher","unstructured":"Rossner, P. et al. Toxic effects of the major components of diesel exhaust in human alveolar basal epithelial cells (A549). Int. J. Mol. Sci. 17 https:\/\/doi.org\/10.3390\/ijms17091393 (2016).","DOI":"10.3390\/ijms17091393"},{"key":"11481_CR41","doi-asserted-by":"publisher","first-page":"117","DOI":"10.3389\/fimmu.2014.00117","volume":"5","author":"R Pacheco","year":"2014","unstructured":"Pacheco, R., Contreras, F. & Zouali, M. The dopaminergic system in autoimmune diseases. Front. Immunol. 5, 117. https:\/\/doi.org\/10.3389\/fimmu.2014.00117 (2014).","journal-title":"Front. Immunol."},{"key":"11481_CR42","doi-asserted-by":"publisher","first-page":"1964","DOI":"10.1016\/j.neurobiolaging.2009.12.014","volume":"32","author":"S Luchetti","year":"2011","unstructured":"Luchetti, S. et al. Neurosteroid biosynthetic pathways changes in prefrontal cortex in alzheimer\u2019s disease. Neurobiol. Aging. 32, 1964\u20131976. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2009.12.014 (2011).","journal-title":"Neurobiol. Aging"},{"key":"11481_CR43","doi-asserted-by":"publisher","unstructured":"Zhang, Q. et al. The classification and prediction of ferroptosis-related genes in ALS: A pilot study. Front. Genet. 13 https:\/\/doi.org\/10.3389\/fgene.2022.919188 (2022).","DOI":"10.3389\/fgene.2022.919188"},{"key":"11481_CR44","doi-asserted-by":"publisher","first-page":"e0280989","DOI":"10.1371\/journal.pone.0280989","volume":"18","author":"W Liu","year":"2023","unstructured":"Liu, W., Zhang, F., Yang, K. & Yan, Y. Comprehensive analysis regarding the prognostic significance of downregulated ferroptosis-related gene AKR1C2 in gastric cancer and its underlying roles in immune response. PloS One. 18, e0280989. https:\/\/doi.org\/10.1371\/journal.pone.0280989 (2023).","journal-title":"PLoS One"},{"key":"11481_CR45","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1111\/cas.13517","volume":"109","author":"H Ide","year":"2018","unstructured":"Ide, H. et al. Modulation of AKR1C2 by Curcumin decreases testosterone production in prostate cancer. Cancer Sci. 109, 1230\u20131238. https:\/\/doi.org\/10.1111\/cas.13517 (2018).","journal-title":"Cancer Sci."},{"key":"11481_CR46","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.pneurobio.2013.10.004","volume":"112","author":"S Ghavami","year":"2014","unstructured":"Ghavami, S. et al. Autophagy and apoptosis dysfunction in neurodegenerative disorders. Prog. Neurobiol. 112, 24\u201349. https:\/\/doi.org\/10.1016\/j.pneurobio.2013.10.004 (2014).","journal-title":"Prog. Neurobiol."},{"key":"11481_CR47","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1080\/15548627.2022.2062112","volume":"19","author":"Y Xu","year":"2023","unstructured":"Xu, Y. & Wan, W. Acetylation in the regulation of autophagy. Autophagy. 19, 379\u2013387. https:\/\/doi.org\/10.1080\/15548627.2022.2062112 (2023).","journal-title":"Autophagy"},{"key":"11481_CR48","doi-asserted-by":"publisher","first-page":"1330","DOI":"10.1080\/15548627.2016.1185590","volume":"12","author":"X Cheng","year":"2016","unstructured":"Cheng, X. et al. Structural basis of FYCO1 and MAP1LC3A interaction reveals a novel binding mode for Atg8-family proteins. Autophagy. 12, 1330\u20131339. https:\/\/doi.org\/10.1080\/15548627.2016.1185590 (2016).","journal-title":"Autophagy"},{"key":"11481_CR49","doi-asserted-by":"publisher","first-page":"1428","DOI":"10.1038\/s41418-018-0219-z","volume":"26","author":"A Rakovic","year":"2019","unstructured":"Rakovic, A. et al. PINK1-dependent mitophagy is driven by the UPS and can occur independently of LC3 conversion. Cell Death Differ. 26, 1428\u20131441. https:\/\/doi.org\/10.1038\/s41418-018-0219-z (2019).","journal-title":"Cell Death Differ."},{"key":"11481_CR50","doi-asserted-by":"publisher","first-page":"2997","DOI":"10.1080\/15548627.2023.2234797","volume":"19","author":"L Mei","year":"2023","unstructured":"Mei, L. et al. Tethering ATG16L1 or LC3 induces targeted autophagic degradation of protein aggregates and mitochondria. Autophagy. 19, 2997\u20133013. https:\/\/doi.org\/10.1080\/15548627.2023.2234797 (2023).","journal-title":"Autophagy"},{"key":"11481_CR51","doi-asserted-by":"publisher","first-page":"e13522","DOI":"10.1111\/acel.13522","volume":"20","author":"HY Tu","year":"2021","unstructured":"Tu, H. Y. et al. \u03b1-synuclein suppresses microglial autophagy and promotes neurodegeneration in a mouse model of Parkinson\u2019s disease. Aging Cell. 20, e13522. https:\/\/doi.org\/10.1111\/acel.13522 (2021).","journal-title":"Aging Cell."},{"key":"11481_CR52","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1080\/15548627.2020.1725377","volume":"17","author":"RQ Yao","year":"2021","unstructured":"Yao, R. Q., Ren, C., Xia, Z. F. & Yao, Y. M. Organelle-specific autophagy in inflammatory diseases: a potential therapeutic target underlying the quality control of multiple organelles. Autophagy. 17, 385\u2013401. https:\/\/doi.org\/10.1080\/15548627.2020.1725377 (2021).","journal-title":"Autophagy"},{"key":"11481_CR53","doi-asserted-by":"publisher","first-page":"e70130","DOI":"10.1096\/fj.202402126R","volume":"38","author":"X Chen","year":"2024","unstructured":"Chen, X. et al. LC3-associated phagocytosis and human diseases: insights from mechanisms to therapeutic potential. FASEB J. 38, e70130. https:\/\/doi.org\/10.1096\/fj.202402126R (2024).","journal-title":"FASEB J."},{"key":"11481_CR54","doi-asserted-by":"publisher","first-page":"105000","DOI":"10.1016\/j.neuint.2021.105000","volume":"145","author":"Y Wu","year":"2021","unstructured":"Wu, Y., Jiao, Z., Wan, Z. & Qu, S. Role of autophagy and oxidative stress to astrocytes in fenpropathrin-induced Parkinson-like damage. Neurochem. Int. 145, 105000. https:\/\/doi.org\/10.1016\/j.neuint.2021.105000 (2021).","journal-title":"Neurochem. Int."},{"key":"11481_CR55","doi-asserted-by":"publisher","first-page":"109909","DOI":"10.1016\/j.neuropharm.2024.109909","volume":"250","author":"HO Abou-Hany","year":"2024","unstructured":"Abou-Hany, H. O., El-Sherbiny, M., Elshaer, S., Said, E. & Moustafa, T. Neuro-modulatory impact of felodipine against experimentally-induced Parkinson\u2019s disease: possible contribution of PINK1-Parkin mitophagy pathway. Neuropharmacology. 250, 109909. https:\/\/doi.org\/10.1016\/j.neuropharm.2024.109909 (2024).","journal-title":"Neuropharmacology"},{"key":"11481_CR56","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.brainresbull.2017.03.009","volume":"133","author":"A Anandhan","year":"2017","unstructured":"Anandhan, A. et al. Metabolic dysfunction in parkinson\u2019s disease: bioenergetics, redox homeostasis and central carbon metabolism. Brain Res. Bull. 133, 12\u201330. https:\/\/doi.org\/10.1016\/j.brainresbull.2017.03.009 (2017).","journal-title":"Brain Res. Bull."},{"key":"11481_CR57","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1186\/s13024-017-0225-5","volume":"12","author":"K Belarbi","year":"2017","unstructured":"Belarbi, K., Cuvelier, E., Dest\u00e9e, A., Gressier, B. & Chartier-Harlin, M. C. NADPH oxidases in Parkinson\u2019s disease: a systematic review. Mol. Neurodegener. 12, 84. https:\/\/doi.org\/10.1186\/s13024-017-0225-5 (2017).","journal-title":"Mol. Neurodegener."},{"key":"11481_CR58","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.nbd.2015.04.020","volume":"84","author":"CA Cobb","year":"2015","unstructured":"Cobb, C. A. & Cole, M. P. Oxidative and nitrative stress in neurodegeneration. Neurobiol. Dis. 84, 4\u201321. https:\/\/doi.org\/10.1016\/j.nbd.2015.04.020 (2015).","journal-title":"Neurobiol. Dis."},{"key":"11481_CR59","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/b978-0-12-385883-2.00005-9","volume":"107","author":"LJ Martin","year":"2012","unstructured":"Martin, L. J. Biology of mitochondria in neurodegenerative diseases. Prog. Mol. Biol. Transl. Sci. 107, 355\u2013415. https:\/\/doi.org\/10.1016\/b978-0-12-385883-2.00005-9 (2012).","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"11481_CR60","doi-asserted-by":"publisher","first-page":"102926","DOI":"10.1016\/j.redox.2023.102926","volume":"67","author":"CN Okoye","year":"2023","unstructured":"Okoye, C. N., Koren, S. A. & Wojtovich, A. P. Mitochondrial complex I ROS production and redox signaling in hypoxia. Redox Biol. 67, 102926. https:\/\/doi.org\/10.1016\/j.redox.2023.102926 (2023).","journal-title":"Redox Biol."},{"key":"11481_CR61","doi-asserted-by":"publisher","unstructured":"Pajares, M., I. R., A., Manda, G., Bosc\u00e1, L. & Cuadrado, A. Inflammation in Parkinson\u2019s disease: mechanisms and therapeutic implications. Cells. 9 https:\/\/doi.org\/10.3390\/cells9071687 (2020).","DOI":"10.3390\/cells9071687"},{"key":"11481_CR62","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1111\/j.1365-2567.2011.03458.x","volume":"133","author":"B Alarc\u00f3n","year":"2011","unstructured":"Alarc\u00f3n, B., Mestre, D. & Mart\u00ednez-Mart\u00edn, N. The immunological synapse: a cause or consequence of T-cell receptor triggering? Immunology. 133, 420\u2013425. https:\/\/doi.org\/10.1111\/j.1365-2567.2011.03458.x (2011).","journal-title":"Immunology"},{"key":"11481_CR63","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1093\/intimm\/dxp033","volume":"21","author":"K Nakano","year":"2009","unstructured":"Nakano, K. et al. Dopamine released by dendritic cells polarizes Th2 differentiation. Int. Immunol. 21, 645\u2013654. https:\/\/doi.org\/10.1093\/intimm\/dxp033 (2009).","journal-title":"Int. Immunol."},{"key":"11481_CR64","doi-asserted-by":"publisher","unstructured":"Lei, C. et al. Identification of necroptosis-related genes in Parkinson\u2019s disease by integrated bioinformatics analysis and experimental validation. Front. NeuroSci. 17 https:\/\/doi.org\/10.3389\/fnins.2023.1097293 (2023).","DOI":"10.3389\/fnins.2023.1097293"},{"key":"11481_CR65","doi-asserted-by":"publisher","first-page":"2371","DOI":"10.2147\/ijgm.S456942","volume":"17","author":"Y Chen","year":"2024","unstructured":"Chen, Y. et al. Integrated bioinformatics analysis for revealing CBL is a potential diagnosing biomarker and related immune infiltration in parkinson\u2019s disease. Int. J. Gen. Med. 17, 2371\u20132386. https:\/\/doi.org\/10.2147\/ijgm.S456942 (2024).","journal-title":"Int. J. Gen. Med."},{"key":"11481_CR66","doi-asserted-by":"publisher","first-page":"593026","DOI":"10.3389\/fphys.2020.593026","volume":"11","author":"S Al-Bachari","year":"2020","unstructured":"Al-Bachari, S., Naish, J. H., Parker, G. J. M., Emsley, H. C. A. & Parkes, L. M. Blood\u2013Brain barrier leakage is increased in Parkinson\u2019s disease. Front. Physiol. 11, 593026. https:\/\/doi.org\/10.3389\/fphys.2020.593026 (2020).","journal-title":"Front. Physiol."},{"key":"11481_CR67","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1038\/nrneurol.2016.88","volume":"12","author":"C Lange","year":"2016","unstructured":"Lange, C., Storkebaum, E., de Almod\u00f3var, C. R., Dewerchin, M. & Carmeliet, P. Vascular endothelial growth factor: a neurovascular target in neurological diseases. Nat. Rev. Neurol. 12, 439\u2013454. https:\/\/doi.org\/10.1038\/nrneurol.2016.88 (2016).","journal-title":"Nat. Rev. Neurol."},{"key":"11481_CR68","doi-asserted-by":"publisher","first-page":"749026","DOI":"10.3389\/fnagi.2021.749026","volume":"13","author":"J Ouellette","year":"2021","unstructured":"Ouellette, J. & Lacoste, B. From neurodevelopmental to neurodegenerative disorders: the vascular continuum. Front. Aging Neurosci. 13, 749026. https:\/\/doi.org\/10.3389\/fnagi.2021.749026 (2021).","journal-title":"Front. Aging Neurosci."},{"key":"11481_CR69","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1136\/bmj.2.5512.487","volume":"2","author":"Florey","year":"1966","unstructured":"Florey. The endothelial cell. Br. Med. J. 2, 487\u2013490. https:\/\/doi.org\/10.1136\/bmj.2.5512.487 (1966).","journal-title":"Br. Med. J."},{"key":"11481_CR70","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1007\/s004010000195","volume":"100","author":"E Farkas","year":"2000","unstructured":"Farkas, E., De Jong, G. I., de Vos, R. A., Steur, J., Luiten, P. G. & E. N. & Pathological features of cerebral cortical capillaries are doubled in Alzheimer\u2019s disease and parkinson\u2019s disease. Acta Neuropathol. 100, 395\u2013402. https:\/\/doi.org\/10.1007\/s004010000195 (2000).","journal-title":"Acta Neuropathol."},{"key":"11481_CR71","doi-asserted-by":"publisher","first-page":"821","DOI":"10.3233\/jpd-140454","volume":"5","author":"P Yang","year":"2015","unstructured":"Yang, P. et al. String vessel formation is increased in the brain of Parkinson disease. J. Parkinson\u2019s Dis. 5, 821\u2013836. https:\/\/doi.org\/10.3233\/jpd-140454 (2015).","journal-title":"J. Parkinson\u2019s Dis."},{"key":"11481_CR72","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.neuint.2019.04.005","volume":"128","author":"HL McConnell","year":"2019","unstructured":"McConnell, H. L., Li, Z., Woltjer, R. L. & Mishra, A. Astrocyte dysfunction and neurovascular impairment in neurological disorders: correlation or causation? Neurochem. Int. 128, 70\u201384. https:\/\/doi.org\/10.1016\/j.neuint.2019.04.005 (2019).","journal-title":"Neurochem. Int."},{"key":"11481_CR73","doi-asserted-by":"crossref","unstructured":"Nagatsu, T., Mogi, M., Ichinose, H. & Togari, A. Cytokines in Parkinson\u2019s disease. J. Neural Trans. Suppl. 143\u2013151 (2000).","DOI":"10.1007\/978-3-7091-6284-2_12"},{"key":"11481_CR74","doi-asserted-by":"publisher","unstructured":"Dolgacheva, L. P., Zinchenko, V. P. & Goncharov, N. V. Molecular and cellular interactions in pathogenesis of sporadic Parkinson disease. Int. J. Mol. Sci. 23 https:\/\/doi.org\/10.3390\/ijms232113043 (2022).","DOI":"10.3390\/ijms232113043"},{"key":"11481_CR75","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1111\/j.1750-3639.2012.00628.x","volume":"23","author":"J Guan","year":"2013","unstructured":"Guan, J. et al. Vascular degeneration in Parkinson\u2019s disease. Brain Pathol. 23, 154\u2013164. https:\/\/doi.org\/10.1111\/j.1750-3639.2012.00628.x (2013).","journal-title":"Brain Pathol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-11481-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-11481-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-11481-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T16:25:10Z","timestamp":1752596710000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-11481-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,15]]},"references-count":75,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["11481"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-11481-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,15]]},"assertion":[{"value":"19 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This study was reviewed and approved by the Experimental Animal Ethics Committee of Chifeng Municipal Hospital (Date: 1 May 2024; No: CFMH-LAEC-202405-01). We confirm that all animal experiments adhered to international ethical standards.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"25610"}}