{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T02:37:19Z","timestamp":1783478239811,"version":"3.55.0"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-21576-4","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T14:46:47Z","timestamp":1761662807000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Machine learning identifies lactate metabolism biomarkers and deciphers immune infiltration landscapes in Parkinson\u2019s disease"],"prefix":"10.1038","volume":"15","author":[{"given":"Hongda","family":"Lv","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LiNa","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyi","family":"Miao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingdian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanhua","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"21576_CR1","doi-asserted-by":"publisher","first-page":"2284","DOI":"10.1016\/s0140-6736(21)00218-x","volume":"397","author":"BR Bloem","year":"2021","unstructured":"Bloem, B. R., Okun, M. S. & Klein, C. Parkinson\u2019s disease. Lancet 397, 2284\u20132303. https:\/\/doi.org\/10.1016\/s0140-6736(21)00218-x (2021).","journal-title":"Lancet"},{"key":"21576_CR2","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. https:\/\/doi.org\/10.1016\/s0140-6736(23)01478-2 (2024).","journal-title":"Lancet"},{"key":"21576_CR3","doi-asserted-by":"publisher","unstructured":"Franco, R., Garrig\u00f3s, C., Lillo, J. & Rivas-Santisteban, R. The potential of metabolomics to find proper biomarkers for addressing the neuroprotective efficacy of drugs aimed at delaying Parkinson\u2019s and Alzheimer\u2019s disease progression. Cells 13 https:\/\/doi.org\/10.3390\/cells13151288 (2024).","DOI":"10.3390\/cells13151288"},{"key":"21576_CR4","doi-asserted-by":"publisher","first-page":"702639","DOI":"10.3389\/fnagi.2021.702639","volume":"13","author":"U Ganguly","year":"2021","unstructured":"Ganguly, U. et al. Alpha-synuclein as a biomarker of parkinson\u2019s disease: good, but not good enough. Front. Aging Neurosci. 13, 702639. https:\/\/doi.org\/10.3389\/fnagi.2021.702639 (2021).","journal-title":"Front. Aging Neurosci."},{"key":"21576_CR5","doi-asserted-by":"publisher","first-page":"69","DOI":"10.4103\/1673-5374.374142","volume":"19","author":"C Yang","year":"2024","unstructured":"Yang, C., Pan, R. Y., Guan, F. & Yuan, Z. Lactate metabolism in neurodegenerative diseases. Neural Regen Res. 19, 69\u201374. https:\/\/doi.org\/10.4103\/1673-5374.374142 (2024).","journal-title":"Neural Regen Res."},{"key":"21576_CR6","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1038\/s41418-024-01427-x","volume":"32","author":"L Zhao","year":"2025","unstructured":"Zhao, L. et al. Lactate dehydrogenase B noncanonically promotes ferroptosis defense in KRAS-driven lung cancer. Cell. Death Differ. 32, 632\u2013645. https:\/\/doi.org\/10.1038\/s41418-024-01427-x (2025).","journal-title":"Cell. Death Differ."},{"key":"21576_CR7","doi-asserted-by":"publisher","first-page":"102032","DOI":"10.1016\/j.arr.2023.102032","volume":"90","author":"H Yu","year":"2023","unstructured":"Yu, H. et al. Metabolic reprogramming and polarization of microglia in parkinson\u2019s disease: role of inflammasome and iron. Ageing Res. Rev. 90, 102032. https:\/\/doi.org\/10.1016\/j.arr.2023.102032 (2023).","journal-title":"Ageing Res. Rev."},{"key":"21576_CR8","doi-asserted-by":"publisher","unstructured":"Cai, B., Zhong, L., Liu, Y., Xu, Q. & Chen, T. \u03b4-Opioid receptor activation inhibits ferroptosis by activating the Nrf2 pathway in MPTP-induced Parkinson disease models. Evid. Based Complement. Alternat Med. 2023 (4130937). https:\/\/doi.org\/10.1155\/2023\/4130937 (2023).","DOI":"10.1155\/2023\/4130937"},{"key":"21576_CR9","doi-asserted-by":"publisher","first-page":"101684","DOI":"10.1016\/j.xcrm.2024.101684","volume":"5","author":"B Lian","year":"2024","unstructured":"Lian, B. et al. SIRT1 improves lactate homeostasis in the brain to alleviate parkinsonism via deacetylation and Inhibition of PKM2. Cell. Rep. Med. 5, 101684. https:\/\/doi.org\/10.1016\/j.xcrm.2024.101684 (2024).","journal-title":"Cell. Rep. Med."},{"key":"21576_CR10","doi-asserted-by":"publisher","first-page":"1506849","DOI":"10.3389\/fonc.2024.1506849","volume":"14","author":"K Sun","year":"2024","unstructured":"Sun, K. et al. Crosstalk between lactate and tumor-associated immune cells: clinical relevance and insight. Front. Oncol. 14, 1506849. https:\/\/doi.org\/10.3389\/fonc.2024.1506849 (2024).","journal-title":"Front. Oncol."},{"key":"21576_CR11","doi-asserted-by":"publisher","first-page":"3702","DOI":"10.1016\/j.febslet.2015.10.021","volume":"589","author":"D Haddad","year":"2015","unstructured":"Haddad, D. & Nakamura, K. Understanding the susceptibility of dopamine neurons to mitochondrial stressors in parkinson\u2019s disease. FEBS Lett. 589, 3702\u20133713. https:\/\/doi.org\/10.1016\/j.febslet.2015.10.021 (2015).","journal-title":"FEBS Lett."},{"key":"21576_CR12","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1038\/s41419-023-06251-8","volume":"14","author":"O Lurette","year":"2023","unstructured":"Lurette, O. et al. Aggregation of alpha-synuclein disrupts mitochondrial metabolism and induce mitophagy via Cardiolipin externalization. Cell. Death Dis. 14, 729. https:\/\/doi.org\/10.1038\/s41419-023-06251-8 (2023).","journal-title":"Cell. Death Dis."},{"key":"21576_CR13","doi-asserted-by":"publisher","unstructured":"Borbolis, F., Ploumi, C. & Palikaras, K. Calcium-mediated regulation of mitophagy: implications in neurodegenerative diseases. NPJ Metab. Health Dis. 3 https:\/\/doi.org\/10.1038\/s44324-025-00049-2 (2025).","DOI":"10.1038\/s44324-025-00049-2"},{"key":"21576_CR14","doi-asserted-by":"publisher","first-page":"2521","DOI":"10.4103\/1673-5374.313057","volume":"16","author":"BY Wang","year":"2021","unstructured":"Wang, B. Y. et al. Stress increases MHC-I expression in dopaminergic neurons and induces autoimmune activation in parkinson\u2019s disease. Neural Regen Res. 16, 2521\u20132527. https:\/\/doi.org\/10.4103\/1673-5374.313057 (2021).","journal-title":"Neural Regen Res."},{"key":"21576_CR15","doi-asserted-by":"publisher","first-page":"115154","DOI":"10.1016\/j.chaos.2024.115154","volume":"185","author":"Z Cao","year":"2024","unstructured":"Cao, Z., Du, L., Zhang, H., Shen, Z. & Deng, Z. Double-edged effect of astrocyte in the transition of physiopathological States in parkinson\u2019s disease. Chaos Solitons Fractals. 185, 115154. https:\/\/doi.org\/10.1016\/j.chaos.2024.115154 (2024).","journal-title":"Chaos Solitons Fractals"},{"key":"21576_CR16","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.4103\/1673-5374.385843","volume":"19","author":"T Shen","year":"2024","unstructured":"Shen, T. et al. TREM-1 mediates interaction between substantia Nigra microglia and peripheral neutrophils. Neural Regen Res. 19, 1375\u20131384. https:\/\/doi.org\/10.4103\/1673-5374.385843 (2024).","journal-title":"Neural Regen Res."},{"key":"21576_CR17","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.neuroscience.2024.06.023","volume":"552","author":"S Liu","year":"2024","unstructured":"Liu, S. & Zhou, S. Lactate: a new target for brain disorders. Neuroscience 552, 100\u2013111. https:\/\/doi.org\/10.1016\/j.neuroscience.2024.06.023 (2024).","journal-title":"Neuroscience"},{"key":"21576_CR18","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1038\/s41586-019-1678-1","volume":"574","author":"D Zhang","year":"2019","unstructured":"Zhang, D. et al. Metabolic regulation of gene expression by histone lactylation. Nature 574, 575\u2013580. https:\/\/doi.org\/10.1038\/s41586-019-1678-1 (2019).","journal-title":"Nature"},{"key":"21576_CR19","doi-asserted-by":"publisher","unstructured":"Holmes, S. E. et al. Synaptic loss and its association with symptom severity in Parkinson\u2019s disease. NPJ Parkinsons Dis. 10 https:\/\/doi.org\/10.1038\/s41531-024-00655-9 (2024).","DOI":"10.1038\/s41531-024-00655-9"},{"key":"21576_CR20","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":"21576_CR21","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. 28, 1947\u20131951. https:\/\/doi.org\/10.1002\/pro.3715 (2019).","journal-title":"Protein Sci."},{"key":"21576_CR22","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":"21576_CR23","doi-asserted-by":"publisher","first-page":"2192","DOI":"10.1093\/hmg\/ddad048","volume":"32","author":"R Asadollahi","year":"2023","unstructured":"Asadollahi, R. et al. Pathogenic SCN2A variants cause early-stage dysfunction in patient-derived neurons. Hum. Mol. Genet. 32, 2192\u20132204. https:\/\/doi.org\/10.1093\/hmg\/ddad048 (2023).","journal-title":"Hum. Mol. Genet."},{"key":"21576_CR24","doi-asserted-by":"publisher","first-page":"539","DOI":"10.2174\/1570159x16666180508113025","volume":"17","author":"B Wang","year":"2019","unstructured":"Wang, B. & Wang, X. P. Does ceruloplasmin defend against neurodegenerative diseases? Curr. Neuropharmacol. 17, 539\u2013549. https:\/\/doi.org\/10.2174\/1570159x16666180508113025 (2019).","journal-title":"Curr. Neuropharmacol."},{"key":"21576_CR25","doi-asserted-by":"publisher","first-page":"140789","DOI":"10.1016\/j.ijbiomac.2025.140789","volume":"304","author":"R Soni","year":"2025","unstructured":"Soni, R. & Shah, J. Unveiling the significance of synaptic proteins in parkinson\u2019s pathogenesis: A review. Int. J. Biol. Macromol. 304, 140789. https:\/\/doi.org\/10.1016\/j.ijbiomac.2025.140789 (2025).","journal-title":"Int. J. Biol. Macromol."},{"key":"21576_CR26","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1002\/med.22091","volume":"45","author":"G Bellini","year":"2025","unstructured":"Bellini, G. et al. \u03b1-Synuclein in parkinson\u2019s disease: from bench to bedside. Med. Res. Rev. 45, 909\u2013946. https:\/\/doi.org\/10.1002\/med.22091 (2025).","journal-title":"Med. Res. Rev."},{"key":"21576_CR27","doi-asserted-by":"publisher","first-page":"107321","DOI":"10.1016\/j.parkreldis.2025.107321","volume":"133","author":"K Dimoula","year":"2025","unstructured":"Dimoula, K., Papagiannakis, N., Maniati, M., Stefanis, L. & Emmanouilidou, E. Aggregated \u03b1-synuclein in erythrocytes as a potential biomarker for idiopathic parkinson\u2019s disease. Parkinsonism Relat. Disord. 133, 107321. https:\/\/doi.org\/10.1016\/j.parkreldis.2025.107321 (2025).","journal-title":"Parkinsonism Relat. Disord"},{"key":"21576_CR28","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.3389\/fphar.2019.01494","volume":"10","author":"NE Chambers","year":"2019","unstructured":"Chambers, N. E., Lanza, K. & Bishop, C. Pedunculopontine nucleus degeneration contributes to both motor and non-motor symptoms of parkinson\u2019s disease. Front. Pharmacol. 10, 1494. https:\/\/doi.org\/10.3389\/fphar.2019.01494 (2019).","journal-title":"Front. Pharmacol."},{"key":"21576_CR29","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.3389\/fphar.2019.01294","volume":"10","author":"A Murueta-Goyena","year":"2019","unstructured":"Murueta-Goyena, A., Andikoetxea, A., G\u00f3mez-Esteban, J. C. & Gabilondo, I. Contribution of the GABAergic system to non-motor manifestations in premotor and early stages of parkinson\u2019s disease. Front. Pharmacol. 10, 1294. https:\/\/doi.org\/10.3389\/fphar.2019.01294 (2019).","journal-title":"Front. Pharmacol."},{"key":"21576_CR30","doi-asserted-by":"publisher","first-page":"14","DOI":"10.3389\/fnmol.2019.00014","volume":"12","author":"S Chen","year":"2019","unstructured":"Chen, S. et al. 27-Hydroxycholesterol contributes to lysosomal membrane permeabilization-mediated pyroptosis in co-cultured SH-SY5Y cells and C6 cells. Front. Mol. Neurosci. 12, 14. https:\/\/doi.org\/10.3389\/fnmol.2019.00014 (2019).","journal-title":"Front. Mol. Neurosci."},{"key":"21576_CR31","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1126\/science.aam9080","volume":"357","author":"LF Burbulla","year":"2017","unstructured":"Burbulla, L. F. et al. Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in parkinson\u2019s disease. Science 357, 1255\u20131261. https:\/\/doi.org\/10.1126\/science.aam9080 (2017).","journal-title":"Science"},{"key":"21576_CR32","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1172\/jci88647","volume":"127","author":"RA Taylor","year":"2017","unstructured":"Taylor, R. A. et al. TGF-\u03b21 modulates microglial phenotype and promotes recovery after intracerebral hemorrhage. J. Clin. Invest. 127, 280\u2013292. https:\/\/doi.org\/10.1172\/jci88647 (2017).","journal-title":"J. Clin. Invest."},{"key":"21576_CR33","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/nature21029","volume":"541","author":"SA Liddelow","year":"2017","unstructured":"Liddelow, S. A. et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541, 481\u2013487. https:\/\/doi.org\/10.1038\/nature21029 (2017).","journal-title":"Nature"},{"key":"21576_CR34","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1146\/annurev-immunol-101921-035639","volume":"41","author":"SS Bohlson","year":"2023","unstructured":"Bohlson, S. S. & Tenner, A. J. Complement in the brain: contributions to neuroprotection, neuronal plasticity, and neuroinflammation. Annu. Rev. Immunol. 41, 431\u2013452. https:\/\/doi.org\/10.1146\/annurev-immunol-101921-035639 (2023).","journal-title":"Annu. Rev. Immunol."},{"key":"21576_CR35","doi-asserted-by":"publisher","unstructured":"Li, X., He, Y., Hao, C., Li, X. & Li, X. Weighted gene correlation network analysis reveals novel regulatory modules associated with recurrent early pregnancy loss. Biosci. Rep. 40 https:\/\/doi.org\/10.1042\/bsr20193938 (2020).","DOI":"10.1042\/bsr20193938"},{"key":"21576_CR36","doi-asserted-by":"publisher","first-page":"20","DOI":"10.17712\/nsj.2025.1.20230112","volume":"30","author":"W Liang","year":"2025","unstructured":"Liang, W. et al. Analysis of key LncRNA related to parkinson\u2019s disease based on gene co-expression weight networks. Neurosciences (Riyadh). 30, 20\u201329. https:\/\/doi.org\/10.17712\/nsj.2025.1.20230112 (2025).","journal-title":"Neurosciences (Riyadh)"},{"key":"21576_CR37","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.neuroscience.2024.02.018","volume":"544","author":"HW Deng","year":"2024","unstructured":"Deng, H. W. et al. Revealing novel genes related to parkinson\u2019s disease pathogenesis and Establishing an associated model. Neuroscience 544, 64\u201374. https:\/\/doi.org\/10.1016\/j.neuroscience.2024.02.018 (2024).","journal-title":"Neuroscience"},{"key":"21576_CR38","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1038\/s41590-024-02074-7","volume":"26","author":"J Shen","year":"2025","unstructured":"Shen, J. et al. Short IL-18 generated by caspase-3 cleavage mobilizes NK cells to suppress tumor growth. Nat. Immunol. 26, 416\u2013428. https:\/\/doi.org\/10.1038\/s41590-024-02074-7 (2025).","journal-title":"Nat. Immunol."},{"key":"21576_CR39","doi-asserted-by":"publisher","unstructured":"Ren, W. et al. Polymorphisms of KCNJ6 Gene and their correlation with immune indicators in Yaks (Bos grunniens). Biomolecules 14, (2024). https:\/\/doi.org\/10.3390\/biom14121576","DOI":"10.3390\/biom14121576"},{"key":"21576_CR40","doi-asserted-by":"publisher","first-page":"2642","DOI":"10.1073\/pnas.1109099109","volume":"109","author":"A Cooper","year":"2012","unstructured":"Cooper, A. et al. Trisomy of the G protein-coupled K\u2009+\u2009channel gene, Kcnj6, affects reward mechanisms, cognitive functions, and synaptic plasticity in mice. Proc. Natl. Acad. Sci. U S A. 109, 2642\u20132647. https:\/\/doi.org\/10.1073\/pnas.1109099109 (2012).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"21576_CR41","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.tins.2013.10.006","volume":"37","author":"R 41 Luj\u00e1n","year":"2014","unstructured":"41 Luj\u00e1n, R., Fernandez de Velasco, M., Aguado, E., Wickman, K. & C. & New insights into the therapeutic potential of Girk channels. Trends Neurosci. 37, 20\u201329. https:\/\/doi.org\/10.1016\/j.tins.2013.10.006 (2014).","journal-title":"Trends Neurosci."},{"key":"21576_CR42","doi-asserted-by":"publisher","first-page":"1639","DOI":"10.1038\/s41598-017-01820-2","volume":"7","author":"F Marron","year":"2017","unstructured":"Marron, F. et al. GIRK2 splice variants and neuronal G protein-gated K(+) channels: implications for channel function and behavior. Sci. Rep. 7, 1639. https:\/\/doi.org\/10.1038\/s41598-017-01820-2 (2017).","journal-title":"Sci. Rep."},{"key":"21576_CR43","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1097\/00001756-200104170-00028","volume":"12","author":"JH Li","year":"2001","unstructured":"Li, J. H., You, Z. D., Song, C. Y., Lu, C. L. & He, C. The expression of G-protein-gated inwardly rectifying K\u2009+\u2009channels GIRK1 and GIRK2 mRNAs in the supraoptic nucleus of the rat and possible role involved. Neuroreport 12, 1007\u20131010. https:\/\/doi.org\/10.1097\/00001756-200104170-00028 (2001).","journal-title":"Neuroreport"},{"key":"21576_CR44","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1002\/ajmg.b.32734","volume":"183","author":"GC Ziegler","year":"2020","unstructured":"Ziegler, G. C. et al. KCNJ6 variants modulate reward-related brain processes and impact executive functions in attention-deficit\/hyperactivity disorder. Am. J. Med. Genet. B Neuropsychiatr Genet. 183, 247\u2013257. https:\/\/doi.org\/10.1002\/ajmg.b.32734 (2020).","journal-title":"Am. J. Med. Genet. B Neuropsychiatr Genet."},{"key":"21576_CR45","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1038\/nature13401","volume":"512","author":"S Schleich","year":"2014","unstructured":"Schleich, S. et al. DENR-MCT-1 promotes translation re-initiation downstream of uORFs to control tissue growth. Nature 512, 208\u2013212. https:\/\/doi.org\/10.1038\/nature13401 (2014).","journal-title":"Nature"},{"key":"21576_CR46","doi-asserted-by":"publisher","first-page":"2059","DOI":"10.1038\/s41467-022-29754-y","volume":"13","author":"B Chen","year":"2022","unstructured":"Chen, B. et al. DENR controls JAK2 translation to induce PD-L1 expression for tumor immune evasion. Nat. Commun. 13, 2059. https:\/\/doi.org\/10.1038\/s41467-022-29754-y (2022).","journal-title":"Nat. Commun."},{"key":"21576_CR47","doi-asserted-by":"publisher","first-page":"350","DOI":"10.2174\/138920212801619214","volume":"13","author":"G Thumann","year":"2012","unstructured":"Thumann, G. Prospectives for gene therapy of retinal degenerations. Curr. Genomics. 13, 350\u2013362. https:\/\/doi.org\/10.2174\/138920212801619214 (2012).","journal-title":"Curr. Genomics"},{"key":"21576_CR48","doi-asserted-by":"publisher","first-page":"2251","DOI":"10.1016\/j.celrep.2016.04.090","volume":"15","author":"MA Haas","year":"2016","unstructured":"Haas, M. A. et al. De Novo mutations in DENR disrupt neuronal development and link congenital neurological disorders to faulty mRNA translation re-initiation. Cell. Rep. 15, 2251\u20132265. https:\/\/doi.org\/10.1016\/j.celrep.2016.04.090 (2016).","journal-title":"Cell. Rep."},{"key":"21576_CR49","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1038\/s41531-024-00777-0","volume":"10","author":"NL Del Rey","year":"2024","unstructured":"Del Rey, N. L. et al. Calbindin and Girk2\/Aldh1a1 define resilient vs vulnerable dopaminergic neurons in a primate parkinson\u2019s disease model. NPJ Parkinsons Dis. 10, 165. https:\/\/doi.org\/10.1038\/s41531-024-00777-0 (2024).","journal-title":"NPJ Parkinsons Dis."},{"key":"21576_CR50","doi-asserted-by":"publisher","first-page":"89","DOI":"10.4067\/s0716-97602011000100012","volume":"44","author":"MP Marzolo","year":"2011","unstructured":"Marzolo, M. P. & Farf\u00e1n, P. New insights into the roles of megalin\/LRP2 and the regulation of its functional expression. Biol. Res. 44, 89\u2013105. https:\/\/doi.org\/10.4067\/s0716-97602011000100012 (2011).","journal-title":"Biol. Res."},{"key":"21576_CR51","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.2174\/1570159x16666180222165418","volume":"16","author":"Q Rui","year":"2018","unstructured":"Rui, Q., Ni, H., Li, D., Gao, R. & Chen, G. The role of LRRK2 in neurodegeneration of Parkinson disease. Curr. Neuropharmacol. 16, 1348\u20131357. https:\/\/doi.org\/10.2174\/1570159x16666180222165418 (2018).","journal-title":"Curr. Neuropharmacol."},{"key":"21576_CR52","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1007\/s12031-023-02182-3","volume":"74","author":"J Wu","year":"2024","unstructured":"Wu, J., Wu, W., Jiang, P., Xu, Y. & Yu, M. Identification of SV2C and DENR as key biomarkers for parkinson\u2019s disease based on bioinformatics, machine learning, and experimental verification. J. Mol. Neurosci. 74, 6. https:\/\/doi.org\/10.1007\/s12031-023-02182-3 (2024).","journal-title":"J. Mol. Neurosci."},{"key":"21576_CR53","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1007\/s00432-023-05573-6","volume":"150","author":"X Xu","year":"2024","unstructured":"Xu, X. et al. Prognosis and immunotherapy response prediction based on M2 macrophage-related genes in colon cancer. J. Cancer Res. Clin. Oncol. 150, 31. https:\/\/doi.org\/10.1007\/s00432-023-05573-6 (2024).","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"21576_CR54","doi-asserted-by":"publisher","first-page":"2378210","DOI":"10.1080\/0886022x.2024.2378210","volume":"46","author":"Y Gu","year":"2024","unstructured":"Gu, Y. et al. M2 macrophage infusion ameliorates diabetic glomerulopathy via the JAK2\/STAT3 pathway in db\/db mice. Ren. Fail. 46, 2378210. https:\/\/doi.org\/10.1080\/0886022x.2024.2378210 (2024).","journal-title":"Ren. Fail."},{"key":"21576_CR55","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1038\/s41416-024-02715-6","volume":"131","author":"JH Rannikko","year":"2024","unstructured":"Rannikko, J. H. & Hollm\u00e9n, M. Clinical landscape of macrophage-reprogramming cancer immunotherapies. Br. J. Cancer. 131, 627\u2013640. https:\/\/doi.org\/10.1038\/s41416-024-02715-6 (2024).","journal-title":"Br. J. Cancer"},{"key":"21576_CR56","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s12896-024-00879-w","volume":"24","author":"Q Pei","year":"2024","unstructured":"Pei, Q. et al. Recombinant Hirudin and PAR-1 regulate macrophage polarisation status in diffuse large B-cell lymphoma. BMC Biotechnol. 24, 55. https:\/\/doi.org\/10.1186\/s12896-024-00879-w (2024).","journal-title":"BMC Biotechnol."},{"key":"21576_CR57","doi-asserted-by":"publisher","first-page":"20220359","DOI":"10.1515\/tnsci-2022-0359","volume":"15","author":"H Cai","year":"2024","unstructured":"Cai, H. et al. Lipid-based nanoparticles for drug delivery in parkinson\u2019s disease. Transl Neurosci. 15, 20220359. https:\/\/doi.org\/10.1515\/tnsci-2022-0359 (2024).","journal-title":"Transl Neurosci."},{"key":"21576_CR58","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1186\/s12864-024-11030-6","volume":"25","author":"S Zhang","year":"2024","unstructured":"Zhang, S. et al. Cross-species single-cell analysis reveals divergence and conservation of peripheral blood mononuclear cells. BMC Genom. 25, 1169. https:\/\/doi.org\/10.1186\/s12864-024-11030-6 (2024).","journal-title":"BMC Genom."},{"key":"21576_CR59","doi-asserted-by":"publisher","first-page":"1216163","DOI":"10.3389\/fnagi.2023.1216163","volume":"15","author":"B Garcia Santa Cruz","year":"2023","unstructured":"Garcia Santa Cruz, B., Husch, A. & Hertel, F. Machine learning models for diagnosis and prognosis of parkinson\u2019s disease using brain imaging: general overview, main challenges, and future directions. Front. Aging Neurosci. 15, 1216163. https:\/\/doi.org\/10.3389\/fnagi.2023.1216163 (2023).","journal-title":"Front. Aging Neurosci."},{"key":"21576_CR60","doi-asserted-by":"publisher","first-page":"977985","DOI":"10.3389\/fnagi.2022.977985","volume":"14","author":"K Dou","year":"2022","unstructured":"Dou, K. et al. Multi-predictor modeling for predicting early parkinson\u2019s disease and non-motor symptoms progression. Front. Aging Neurosci. 14, 977985. https:\/\/doi.org\/10.3389\/fnagi.2022.977985 (2022).","journal-title":"Front. Aging Neurosci."},{"key":"21576_CR61","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/s41531-025-00923-2","volume":"11","author":"T H\u00e4hnel","year":"2025","unstructured":"H\u00e4hnel, T. et al. Predictive modeling to uncover parkinson\u2019s disease characteristics that delay diagnosis. NPJ Parkinsons Dis. 11, 64. https:\/\/doi.org\/10.1038\/s41531-025-00923-2 (2025).","journal-title":"NPJ Parkinsons Dis."},{"key":"21576_CR62","unstructured":"Zhang, X. et al. Multi-view graph convolutional network and its applications on neuroimage analysis for Parkinson\u2019s disease. AMIA Annu. Symp. Proc. 2018, 1147\u20131156 (2018)."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-21576-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-21576-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-21576-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T02:03:50Z","timestamp":1762049030000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-21576-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,28]]},"references-count":62,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["21576"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-21576-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,28]]},"assertion":[{"value":"5 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 October 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"}}],"article-number":"37665"}}