{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T01:07:24Z","timestamp":1770080844592,"version":"3.49.0"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T00:00:00Z","timestamp":1767398400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":30,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"DOI":"10.1186\/s12967-025-07597-7","type":"journal-article","created":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T07:43:18Z","timestamp":1767426198000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcranial direct current stimulation exerts neuroprotective effects in Parkinson\u2019s disease by restoring Mlst8-mediated autophagic homeostasis"],"prefix":"10.1186","volume":"24","author":[{"given":"Zekun","family":"Tian","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Long","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manxia","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keshu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengbiao","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsung-Hsun","family":"Hsieh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojun","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,3]]},"reference":[{"key":"7597_CR1","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1016\/s1474-4422(18)30295-3","volume":"17","author":"Global, regional, and national burden of Parkinson\u2019s disease, 1990-2016. A systematic analysis for the Global burden of disease study 2016","year":"2018","unstructured":"Global, regional, and national burden of Parkinson\u2019s disease, 1990-2016. A systematic analysis for the Global burden of disease study 2016. Lancet Neurol. 2018;17:939\u201353. https:\/\/doi.org\/10.1016\/s1474-4422(18)30295-3.","journal-title":"Lancet Neurol"},{"key":"7597_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 HR, Spillantini MG, Sue CM, Williams-Gray CH. The pathogenesis of Parkinson\u2019s disease. Lancet. 2024;403:293\u2013304. https:\/\/doi.org\/10.1016\/s0140-6736(23)01478-2.","journal-title":"Lancet"},{"key":"7597_CR3","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/s1474-4422(21)00330-6","volume":"21","author":"D Weintraub","year":"2022","unstructured":"Weintraub D, et al. The neuropsychiatry of Parkinson\u2019s disease: advances and challenges. Lancet Neurol. 2022;21:89\u2013102. https:\/\/doi.org\/10.1016\/s1474-4422(21)00330-6.","journal-title":"Lancet Neurol"},{"key":"7597_CR4","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1038\/s41591-024-03428-2","volume":"31","author":"C Moreau","year":"2025","unstructured":"Moreau C, et al. Intracerebroventricular anaerobic dopamine in Parkinson\u2019s disease with L-dopa-related complications: a phase 1\/2 randomized-controlled trial. Nat Med. 2025;31:819\u201328. https:\/\/doi.org\/10.1038\/s41591-024-03428-2.","journal-title":"Nat Med"},{"key":"7597_CR5","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1002\/mds.26354","volume":"30","author":"LV Kalia","year":"2015","unstructured":"Kalia LV, Kalia SK, Lang AE. Disease-modifying strategies for Parkinson\u2019s disease. Mov Disord. 2015;30:1442\u201350. https:\/\/doi.org\/10.1002\/mds.26354.","journal-title":"Mov Disord"},{"key":"7597_CR6","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 HR, Foltynie T. Progress towards therapies for disease modification in Parkinson\u2019s disease. Lancet Neurol. 2021;20:559\u201372. https:\/\/doi.org\/10.1016\/s1474-4422(21)00061-2.","journal-title":"Lancet Neurol"},{"key":"7597_CR7","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/s41582-020-00426-z","volume":"17","author":"JK Krauss","year":"2021","unstructured":"Krauss JK, et al. Technology of deep brain stimulation: current status and future directions. Nat Rev Neurol. 2021;17:75\u201387. https:\/\/doi.org\/10.1038\/s41582-020-00426-z.","journal-title":"Nat Rev Neurol"},{"key":"7597_CR8","doi-asserted-by":"publisher","first-page":"3345","DOI":"10.1038\/s41591-024-03196-z","volume":"30","author":"CR Oehrn","year":"2024","unstructured":"Oehrn CR, et al. Chronic adaptive deep brain stimulation versus conventional stimulation in Parkinson\u2019s disease: a blinded randomized feasibility trial. Nat Med. 2024;30:3345\u201356. https:\/\/doi.org\/10.1038\/s41591-024-03196-z.","journal-title":"Nat Med"},{"key":"7597_CR9","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1038\/s41582-018-0128-2","volume":"15","author":"AM Lozano","year":"2019","unstructured":"Lozano AM, et al. Deep brain stimulation: current challenges and future directions. Nat Rev Neurol. 2019;15:148\u201360. https:\/\/doi.org\/10.1038\/s41582-018-0128-2.","journal-title":"Nat Rev Neurol"},{"key":"7597_CR10","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1016\/s1474-4422(21)00300-8","volume":"20","author":"P Ryvlin","year":"2021","unstructured":"Ryvlin P, Rheims S, Hirsch LJ, Sokolov A, Jehi L. Neuromodulation in epilepsy: state-of-the-art approved therapies. Lancet Neurol. 2021;20:1038\u201347. https:\/\/doi.org\/10.1016\/s1474-4422(21)00300-8.","journal-title":"Lancet Neurol"},{"key":"7597_CR11","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.cell.2020.02.054","volume":"181","author":"SM Won","year":"2020","unstructured":"Won SM, Song E, Reeder JT, Rogers JA. Emerging modalities and implantable technologies for Neuromodulation. Cell. 2020;181:115\u201335. https:\/\/doi.org\/10.1016\/j.cell.2020.02.054.","journal-title":"Cell"},{"key":"7597_CR12","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.tics.2022.11.013","volume":"27","author":"M Wischnewski","year":"2023","unstructured":"Wischnewski M, Alekseichuk I, Opitz A. Neurocognitive, physiological, and biophysical effects of transcranial alternating current stimulation. Trends Cogn Sci. 2023;27:189\u2013205. https:\/\/doi.org\/10.1016\/j.tics.2022.11.013.","journal-title":"Trends Cogn Sci"},{"key":"7597_CR13","doi-asserted-by":"publisher","unstructured":"Nguyen TXD, Mai PT, Chang YJ, Hsieh TH. Effects of transcranial direct current stimulation alone and in combination with rehabilitation therapies on gait and balance among individuals with Parkinson\u2019s disease: a systematic review and meta-analysis. J Neuroeng Rehabil. 2024;21(27). https:\/\/doi.org\/10.1186\/s12984-024-01311-2.","DOI":"10.1186\/s12984-024-01311-2"},{"key":"7597_CR14","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/j.brs.2024.04.001","volume":"17","author":"L Melo","year":"2024","unstructured":"Melo L, Beaupain MC, Ghanavati E, Kuo MF, Nitsche MA. Neurochemical mechanisms underlying serotonergic modulation of neuroplasticity in humans. Brain Stimul. 2024;17:421\u201330. https:\/\/doi.org\/10.1016\/j.brs.2024.04.001.","journal-title":"Brain Stimul"},{"key":"7597_CR15","doi-asserted-by":"publisher","first-page":"104491","DOI":"10.1016\/j.neuint.2019.104491","volume":"129","author":"SB Lee","year":"2019","unstructured":"Lee SB, Youn J, Jang W, Yang HO. Neuroprotective effect of anodal transcranial direct current stimulation on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced neurotoxicity in mice through modulating mitochondrial dynamics. Neurochem Int. 2019;129:104491. https:\/\/doi.org\/10.1016\/j.neuint.2019.104491.","journal-title":"Neurochem Int"},{"key":"7597_CR16","doi-asserted-by":"publisher","first-page":"e70014","DOI":"10.1111\/jnc.70014","volume":"169","author":"M Piccoli","year":"2025","unstructured":"Piccoli M, et al. Direct current stimulation (DCS) modulates lipid metabolism and intercellular vesicular trafficking in SHSY-5Y cell line: implications for Parkinson\u2019s disease. J Neurochem. 2025;169:e70014. https:\/\/doi.org\/10.1111\/jnc.70014.","journal-title":"J Neurochem"},{"key":"7597_CR17","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1016\/j.brs.2020.02.002","volume":"13","author":"XJ Feng","year":"2020","unstructured":"Feng XJ, et al. Early transcranial direct current stimulation treatment exerts neuroprotective effects on 6-OHDA-induced parkinsonism in rats. Brain Stimul. 2020;13:655\u201363. https:\/\/doi.org\/10.1016\/j.brs.2020.02.002.","journal-title":"Brain Stimul"},{"key":"7597_CR18","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1093\/brain\/awad388","volume":"147","author":"Y Chu","year":"2024","unstructured":"Chu Y, et al. Nigrostriatal tau pathology in parkinsonism and Parkinson\u2019s disease. Brain. 2024;147:444\u201357. https:\/\/doi.org\/10.1093\/brain\/awad388.","journal-title":"Brain"},{"key":"7597_CR19","doi-asserted-by":"publisher","unstructured":"Szeg\u0151 \u00c9, M, et al. Intermittent fasting reduces alpha-synuclein pathology and functional decline in a mouse model of Parkinson\u2019s disease. Nat Commun. 2025;16:4470. https:\/\/doi.org\/10.1038\/s41467-025-59249-5.","DOI":"10.1038\/s41467-025-59249-5"},{"key":"7597_CR20","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.neuron.2024.09.015","volume":"113","author":"JE Palmer","year":"2025","unstructured":"Palmer JE, et al. Autophagy, aging, and age-related neurodegeneration. Neuron. 2025;113:29\u201348. https:\/\/doi.org\/10.1016\/j.neuron.2024.09.015.","journal-title":"Neuron"},{"key":"7597_CR21","doi-asserted-by":"publisher","first-page":"2197","DOI":"10.1038\/s41598-021-81693-8","volume":"11","author":"G Sala","year":"2021","unstructured":"Sala G, et al. Direct current stimulation enhances neuronal alpha-synuclein degradation in vitro. Sci Rep. 2021;11:2197. https:\/\/doi.org\/10.1038\/s41598-021-81693-8.","journal-title":"Sci Rep"},{"key":"7597_CR22","doi-asserted-by":"publisher","unstructured":"Guo T, Fang J, Tong ZY, He S, Luo Y. Transcranial direct current stimulation ameliorates cognitive impairment via modulating oxidative stress, inflammation, and autophagy in a rat model of vascular dementia. Front Neurosci. 2020;14(28). https:\/\/doi.org\/10.3389\/fnins.2020.00028.","DOI":"10.3389\/fnins.2020.00028"},{"key":"7597_CR23","doi-asserted-by":"publisher","first-page":"12535","DOI":"10.1523\/jneurosci.1920-10.2010","volume":"30","author":"B Dehay","year":"2010","unstructured":"Dehay B, et al. Pathogenic lysosomal depletion in Parkinson\u2019s disease. J Neurosci. 2010;30:12535\u201344. https:\/\/doi.org\/10.1523\/jneurosci.1920-10.2010.","journal-title":"J Neurosci"},{"key":"7597_CR24","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.4103\/1673-5374.327353","volume":"17","author":"JN Yan","year":"2022","unstructured":"Yan JN, et al. Schwann cells differentiated from skin-derived precursors provide neuroprotection via autophagy inhibition in a cellular model of Parkinson\u2019s disease. Neural Regen Res. 2022;17:1357\u201363. https:\/\/doi.org\/10.4103\/1673-5374.327353.","journal-title":"Neural Regen Res"},{"key":"7597_CR25","doi-asserted-by":"publisher","unstructured":"Kang C, et al. Baicalin alleviates 6-hydroxydopamine-induced neurotoxicity in PC12 cells by down-regulation of microRNA-192-5p. Brain Res. 1708 (2019;84\u201392. https:\/\/doi.org\/10.1016\/j.brainres.2018.12.015.","DOI":"10.1016\/j.brainres.2018.12.015"},{"key":"7597_CR26","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1080\/15548627.2015.1082020","volume":"11","author":"LY Su","year":"2015","unstructured":"Su LY, et al. Melatonin attenuates MPTP-induced neurotoxicity via preventing CDK5-mediated autophagy and SNCA\/\u03b1-synuclein aggregation. Autophagy. 2015;11:1745\u201359. https:\/\/doi.org\/10.1080\/15548627.2015.1082020.","journal-title":"Autophagy"},{"key":"7597_CR27","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1038\/s41580-019-0199-y","volume":"21","author":"GY Liu","year":"2020","unstructured":"Liu GY, Sabatini D. M. mTOR at the nexus of nutrition, growth, ageing and disease. Nat Rev Mol Cell Biol. 2020;21:183\u2013203. https:\/\/doi.org\/10.1038\/s41580-019-0199-y.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"7597_CR28","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1186\/s12943-023-01820-z","volume":"22","author":"A Marques-Ramos","year":"2023","unstructured":"Marques-Ramos A, Cervantes R. Expression of mTOR in normal and pathological conditions. Mol Cancer. 2023;22:112. https:\/\/doi.org\/10.1186\/s12943-023-01820-z.","journal-title":"Mol Cancer"},{"key":"7597_CR29","doi-asserted-by":"publisher","first-page":"e0089923","DOI":"10.1128\/mbio.00899-23","volume":"14","author":"Y Fu","year":"2023","unstructured":"Fu Y, et al. mLST8 is essential for coronavirus replication and regulates its replication through the mTORC1 pathway. mBio. 2023;14:e0089923. https:\/\/doi.org\/10.1128\/mbio.00899-23.","journal-title":"mBio"},{"key":"7597_CR30","doi-asserted-by":"publisher","unstructured":"Bammidi S, et al. MLST8 overexpression in RPE cells disrupts autophagy through novel mechanisms affecting AMD pathogenesis. Autophagy. 2025;1\u20133. https:\/\/doi.org\/10.1080\/15548627.2025.2491097.","DOI":"10.1080\/15548627.2025.2491097"},{"key":"7597_CR31","doi-asserted-by":"publisher","first-page":"e70018","DOI":"10.1111\/acel.70018","volume":"24","author":"O Chowdhury","year":"2025","unstructured":"Chowdhury O, et al. Activated mTOR signaling in the RPE drives EMT, autophagy, and metabolic disruption, resulting in AMD-Like pathology in mice. Aging Cell. 2025;24:e70018. https:\/\/doi.org\/10.1111\/acel.70018.","journal-title":"Aging Cell"},{"key":"7597_CR32","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. 2007;2:141\u201351. https:\/\/doi.org\/10.1038\/nprot.2006.342.","journal-title":"Nat Protoc"},{"key":"7597_CR33","doi-asserted-by":"publisher","first-page":"154250","DOI":"10.1016\/j.phymed.2022.154250","volume":"104","author":"LK Wu","year":"2022","unstructured":"Wu LK, et al. Artemisia leaf extract protects against neuron toxicity by TRPML1 activation and promoting autophagy\/mitophagy clearance in both in vitro and in vivo models of MPP+\/MPTP-induced Parkinson\u2019s disease. Phytomedicine. 2022;104:154250. https:\/\/doi.org\/10.1016\/j.phymed.2022.154250.","journal-title":"Phytomedicine"},{"key":"7597_CR34","doi-asserted-by":"publisher","unstructured":"Hwang DJ, et al. Comparative analysis of dose-dependent neurotoxic response to 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine in C57BL\/6 N mice derived from three different sources. Lab Anim Res. 2019;35(10). https:\/\/doi.org\/10.1186\/s42826-019-0012-2.","DOI":"10.1186\/s42826-019-0012-2"},{"key":"7597_CR35","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/nrn2652","volume":"10","author":"SP Brooks","year":"2009","unstructured":"Brooks SP, Dunnett SB. Tests to assess motor phenotype in mice: a user\u2019s guide. Nat Rev Neurosci. 2009;10:519\u201329. https:\/\/doi.org\/10.1038\/nrn2652.","journal-title":"Nat Rev Neurosci"},{"key":"7597_CR36","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love MI, Huber W, Anders S. Moderated estimation of Fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550. https:\/\/doi.org\/10.1186\/s13059-014-0550-8.","journal-title":"Genome Biol"},{"key":"7597_CR37","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1186\/s13059-019-1910-1","volume":"20","author":"S Kovaka","year":"2019","unstructured":"Kovaka S, et al. Transcriptome assembly from long-read RNA-seq alignments with StringTie2. Genome Biol. 2019;20:278. https:\/\/doi.org\/10.1186\/s13059-019-1910-1.","journal-title":"Genome Biol"},{"key":"7597_CR38","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","volume":"16","author":"G Yu","year":"2012","unstructured":"Yu G, Wang LG, Han Y, He QY. clusterProfiler: an R package for comparing biological themes among gene clusters. Omics. 2012;16:284\u201387. https:\/\/doi.org\/10.1089\/omi.2011.0118.","journal-title":"Omics"},{"key":"7597_CR39","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","volume":"630","author":"J Abramson","year":"2024","unstructured":"Abramson J, et al. Accurate structure prediction of biomolecular interactions with AlphaFold 3. Nature. 2024;630:493\u2013500. https:\/\/doi.org\/10.1038\/s41586-024-07487-w.","journal-title":"Nature"},{"key":"7597_CR40","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaf394","author":"S Ahmad","year":"2025","unstructured":"Ahmad S, et al. The UniProt website API: facilitating programmatic access to protein knowledge. Nucleic Acids Res. 2025. https:\/\/doi.org\/10.1093\/nar\/gkaf394.","journal-title":"Nucleic Acids Res"},{"key":"7597_CR41","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.1038\/nprot.2007.205","volume":"2","author":"B Song","year":"2007","unstructured":"Song B, et al. Application of direct current electric fields to cells and tissues in vitro and modulation of wound electric field in vivo. Nat Protoc. 2007;2:1479\u201389. https:\/\/doi.org\/10.1038\/nprot.2007.205.","journal-title":"Nat Protoc"},{"key":"7597_CR42","doi-asserted-by":"publisher","unstructured":"Ahuja M, et al. Bach1 derepression is neuroprotective in a mouse model of Parkinson\u2019s disease. Proc Natl Acad Sci U S A. 2021;118. https:\/\/doi.org\/10.1073\/pnas.2111643118.","DOI":"10.1073\/pnas.2111643118"},{"key":"7597_CR43","doi-asserted-by":"publisher","unstructured":"Liu N, et al. TRPV4 contributes to er stress and inflammation: implications for Parkinson\u2019s disease. J Neuroinflammation. 2022;19(26). https:\/\/doi.org\/10.1186\/s12974-022-02382-5.","DOI":"10.1186\/s12974-022-02382-5"},{"key":"7597_CR44","doi-asserted-by":"publisher","unstructured":"Sun CP, et al. Kurarinone alleviated Parkinson\u2019s disease via stabilization of epoxyeicosatrienoic acids in animal model. Proc Natl Acad Sci USA. 2022;119. https:\/\/doi.org\/10.1073\/pnas.2118818119.","DOI":"10.1073\/pnas.2118818119"},{"key":"7597_CR45","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1016\/j.cell.2011.10.026","volume":"147","author":"N Mizushima","year":"2011","unstructured":"Mizushima N, Komatsu M. Autophagy: renovation of cells and tissues. Cell. 2011;147:728\u201341. https:\/\/doi.org\/10.1016\/j.cell.2011.10.026.","journal-title":"Cell"},{"key":"7597_CR46","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","volume":"102","author":"A Subramanian","year":"2005","unstructured":"Subramanian A, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 2005;102:15545\u201350. https:\/\/doi.org\/10.1073\/pnas.0506580102.","journal-title":"Proc Natl Acad Sci USA"},{"key":"7597_CR47","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1038\/ng1180","volume":"34","author":"VK Mootha","year":"2003","unstructured":"Mootha VK, et al. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 2003;34:267\u201373. https:\/\/doi.org\/10.1038\/ng1180.","journal-title":"Nat Genet"},{"key":"7597_CR48","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.freeradbiomed.2024.02.023","volume":"216","author":"L Wang","year":"2024","unstructured":"Wang L, et al. Neuroprotective effects of cordycepin on MPTP-induced Parkinson\u2019s disease mice via suppressing PI3K\/AKT\/mTOR and MAPK-mediated neuroinflammation. Free Radic Biol Med. 2024;216:60\u201377. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2024.02.023.","journal-title":"Free Radic Biol Med"},{"key":"7597_CR49","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1080\/15548627.2023.2300922","volume":"20","author":"P Huang","year":"2024","unstructured":"Huang P, et al. MCOLN\/TRPML channels in the regulation of MTORC1 and autophagy. Autophagy. 2024;20:1203\u201304. https:\/\/doi.org\/10.1080\/15548627.2023.2300922.","journal-title":"Autophagy"},{"key":"7597_CR50","doi-asserted-by":"publisher","first-page":"2865","DOI":"10.1038\/s41467-019-10781-1","volume":"10","author":"J Cu\u00e9llar","year":"2019","unstructured":"Cu\u00e9llar J, et al. Structural and functional analysis of the role of the chaperonin CCT in mTOR complex assembly. Nat Commun. 2019;10:2865. https:\/\/doi.org\/10.1038\/s41467-019-10781-1.","journal-title":"Nat Commun"},{"key":"7597_CR51","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/nature12122","volume":"497","author":"H Yang","year":"2013","unstructured":"Yang H, et al. mTOR kinase structure, mechanism and regulation. Nature. 2013;497:217\u201323. https:\/\/doi.org\/10.1038\/nature12122.","journal-title":"Nature"},{"key":"7597_CR52","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1126\/science.aaa3870","volume":"351","author":"CH Aylett","year":"2016","unstructured":"Aylett CH, et al. Architecture of human mTOR complex 1. Science. 2016;351:48\u201352. https:\/\/doi.org\/10.1126\/science.aaa3870.","journal-title":"Science"},{"key":"7597_CR53","doi-asserted-by":"publisher","first-page":"3187","DOI":"10.1007\/s12035-021-02320-1","volume":"58","author":"L Bai","year":"2021","unstructured":"Bai L, et al. Thioredoxin-1 rescues MPP(+)\/MPTP-Induced ferroptosis by increasing glutathione peroxidase 4. Mol Neurobiol. 2021;58:3187\u201397. https:\/\/doi.org\/10.1007\/s12035-021-02320-1.","journal-title":"Mol Neurobiol"},{"key":"7597_CR54","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1038\/nn.2372","volume":"12","author":"LS Tain","year":"2009","unstructured":"Tain LS, et al. Rapamycin activation of 4E-BP prevents parkinsonian dopaminergic neuron loss. Nat Neurosci. 2009;12:1129\u201335. https:\/\/doi.org\/10.1038\/nn.2372.","journal-title":"Nat Neurosci"},{"key":"7597_CR55","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/j.neuroscience.2009.08.014","volume":"164","author":"T Pan","year":"2009","unstructured":"Pan T, et al. Rapamycin protects against rotenone-induced apoptosis through autophagy induction. Neuroscience. 2009;164:541\u201351. https:\/\/doi.org\/10.1016\/j.neuroscience.2009.08.014.","journal-title":"Neuroscience"},{"key":"7597_CR56","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1007\/s10787-023-01141-z","volume":"31","author":"S Kartik","year":"2023","unstructured":"Kartik S, et al. Neuroprotective role of chloroquine via modulation of autophagy and neuroinflammation in MPTP-induced Parkinson\u2019s disease. Inflammopharmacology. 2023;31:927\u201341. https:\/\/doi.org\/10.1007\/s10787-023-01141-z.","journal-title":"Inflammopharmacology"},{"key":"7597_CR57","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1038\/nrn3068","volume":"12","author":"J Bov\u00e9","year":"2011","unstructured":"Bov\u00e9 J, Mart\u00ednez-Vicente M, Vila M. Fighting neurodegeneration with rapamycin: mechanistic insights. Nat Rev Neurosci. 2011;12:437\u201352. https:\/\/doi.org\/10.1038\/nrn3068.","journal-title":"Nat Rev Neurosci"},{"key":"7597_CR58","doi-asserted-by":"publisher","first-page":"102044","DOI":"10.1016\/j.xcrm.2025.102044","volume":"6","author":"J Liu","year":"2025","unstructured":"Liu J, et al. Common and specific effects in brain oscillations and motor symptoms of tDCS and tACS in Parkinson\u2019s disease. Cell Rep Med. 2025;6:102044. https:\/\/doi.org\/10.1016\/j.xcrm.2025.102044.","journal-title":"Cell Rep Med"},{"key":"7597_CR59","doi-asserted-by":"publisher","first-page":"1564","DOI":"10.1056\/NEJMra2022774","volume":"383","author":"N Mizushima","year":"2020","unstructured":"Mizushima N, Levine B. Autophagy in human diseases. N Engl J Med. 2020;383:1564\u201376. https:\/\/doi.org\/10.1056\/NEJMra2022774.","journal-title":"N Engl J Med"},{"key":"7597_CR60","first-page":"261","volume":"31","author":"S Ito","year":"2007","unstructured":"Ito S, Koshikawa N, Mochizuki S, Takenaga K. 3-Methyladenine suppresses cell migration and invasion of HT1080 fibrosarcoma cells through inhibiting phosphoinositide 3-kinases independently of autophagy inhibition. Int J Oncol. 2007;31:261\u201368.","journal-title":"Int J Oncol"},{"key":"7597_CR61","doi-asserted-by":"publisher","first-page":"e35665","DOI":"10.1371\/journal.pone.0035665","volume":"7","author":"H Hou","year":"2012","unstructured":"Hou H, et al. Inhibitors of phosphatidylinositol 3\u2019-kinases promote mitotic cell death in HeLa cells. PLoS One. 2012;7:e35665. https:\/\/doi.org\/10.1371\/journal.pone.0035665.","journal-title":"PLoS One"},{"key":"7597_CR62","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.lfs.2016.06.024","volume":"158","author":"R Libro","year":"2016","unstructured":"Libro R, Bramanti P, Mazzon E. The role of the Wnt canonical signaling in neurodegenerative diseases. Life Sci. 2016;158:78\u201388. https:\/\/doi.org\/10.1016\/j.lfs.2016.06.024.","journal-title":"Life Sci"},{"key":"7597_CR63","doi-asserted-by":"publisher","first-page":"101664","DOI":"10.1016\/j.redox.2020.101664","volume":"36","author":"B Marchetti","year":"2020","unstructured":"Marchetti B. Nrf2\/Wnt resilience orchestrates rejuvenation of glia-neuron dialogue in Parkinson\u2019s disease. Redox Biol. 2020;36:101664. https:\/\/doi.org\/10.1016\/j.redox.2020.101664.","journal-title":"Redox Biol"},{"key":"7597_CR64","doi-asserted-by":"publisher","first-page":"3630","DOI":"10.1007\/s12035-024-04462-4","volume":"62","author":"N Faraji","year":"2025","unstructured":"Faraji N, Ebadpour N, Abavisani M, Gorji A. Unlocking hope: therapeutic advances and approaches in modulating the Wnt pathway for neurodegenerative diseases. Mol Neurobiol. 2025;62:3630\u201352. https:\/\/doi.org\/10.1007\/s12035-024-04462-4.","journal-title":"Mol Neurobiol"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-025-07597-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-025-07597-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-025-07597-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T13:57:32Z","timestamp":1770040652000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12967-025-07597-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,3]]},"references-count":64,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["7597"],"URL":"https:\/\/doi.org\/10.1186\/s12967-025-07597-7","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,3]]},"assertion":[{"value":"1 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All animal procedures were approved by the Institutional Animal Care and Use Committee of Anhui Medical University (Approval ID: LLSC20241410). Analysis code and figure-generation scripts are available from the corresponding author upon reasonable request.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"125"}}