{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T10:17:38Z","timestamp":1788862658450,"version":"build-2803163510"},"reference-count":47,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32560044"],"award-info":[{"award-number":["32560044"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32560044"],"award-info":[{"award-number":["32560044"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Hubei Minzu University","award":["PT082301"],"award-info":[{"award-number":["PT082301"]}]},{"award":["PT082301"],"award-info":[{"award-number":["PT082301"]}],"id":[{"id":"https:\/\/ror.org\/01q349q17","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Selenium-dependent antioxidant systems are critical for neuronal redox balance, but whether Parkinson\u2019s disease (PD) involves systemic selenium deficiency or selective utilization impairment remains unclear. Using Parkinson\u2019s Progression Markers Initiative (PPMI) proteomic data, we identified specific downregulation of glutathione peroxidase 3 (GPX3) in cerebrospinal fluid in PD, suggesting a compartment-specific alteration in GPX3-related antioxidant defense rather than a uniform systemic selenium deficit. Inorganic selenium sources suffer from low bioavailability and narrow therapeutic windows. We therefore developed a selenium-enriched peptide fraction (IPP-Se-F12) via controlled selenization of Idesia polycarpa Maxim. cake meal peptides, and characterized its selenium content, size distribution, and radical-scavenging activity. In SH-SY5Y and nematode models, IPP-Se-F12 attenuated 6-hydroxydopamine (6-OHDA)-induced cell death and rescued locomotor and dopamine-dependent behaviors more effectively than sodium selenite treatment. RNAseq further showed that IPP-Se-F12 treatment was associated with transcriptional changes in dephosphorylation, axon-guidance, and GPX3-centered antioxidant networks, including increased expression of gpx-3 and gpx-5. This study supports IPP-Se-F12 as a plant-derived selenium-associated peptide fraction with protective activity in cellular and nematode models and identifies GPX-related antioxidant regulation as a candidate mechanism for further investigation.<\/jats:p>","DOI":"10.3390\/cells15181628","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T10:00:04Z","timestamp":1788861604000},"page":"1628","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bioactive Selenium Peptides Rescue Dopaminergic Neurodegeneration via Coordinated Signal Remodeling and Redox Reinforcement"],"prefix":"10.3390","volume":"15","author":[{"given":"Xue","family":"Hou","sequence":"first","affiliation":[{"name":"Hubei Engineering Research Center of Selenium Food Nutrition and Health Intelligent Technology, Hubei Minzu University, Enshi 445000, China"},{"name":"College of Biological and Food Engineering, Hubei Minzu University, Enshi 445000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Lin","family":"Luo","sequence":"additional","affiliation":[{"name":"Hubei Engineering Research Center of Selenium Food Nutrition and Health Intelligent Technology, Hubei Minzu University, Enshi 445000, China"},{"name":"College of Biological and Food Engineering, Hubei Minzu University, Enshi 445000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"visualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Ruojia","family":"Li","sequence":"additional","affiliation":[{"name":"Hubei Engineering Research Center of Selenium Food Nutrition and Health Intelligent Technology, Hubei Minzu University, Enshi 445000, China"},{"name":"College of Biological and Food Engineering, Hubei Minzu University, Enshi 445000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"visualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Yuying","family":"Li","sequence":"additional","affiliation":[{"name":"Hubei Engineering Research Center of Selenium Food Nutrition and Health Intelligent Technology, Hubei Minzu University, Enshi 445000, China"},{"name":"College of Biological and Food Engineering, Hubei Minzu University, Enshi 445000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"visualization","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Zhiyong","family":"Wang","sequence":"additional","affiliation":[{"name":"Hubei Engineering Research Center of Selenium Food Nutrition and Health Intelligent Technology, Hubei Minzu University, Enshi 445000, China"},{"name":"College of Biological and Food Engineering, Hubei Minzu University, Enshi 445000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Yangyang","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Westlake University, Hangzhou 310024, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"150185","DOI":"10.1016\/j.ijbiomac.2026.150185","article-title":"Zinc-\u03b12-glycoprotein overexpression attenuates gasdermin D-mediated pyroptosis in dopaminergic neurons by suppressing reactive oxygen species\/mitogen-activated protein kinase signaling","volume":"343","author":"Mo","year":"2026","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1016\/S0140-6736(21)00218-X","article-title":"Parkinson\u2019s disease","volume":"397","author":"Bloem","year":"2021","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"104062","DOI":"10.1016\/j.drudis.2024.104062","article-title":"Selenium-containing compounds: A new hope for innovative treatments in Alzheimer\u2019s disease and Parkinson\u2019s disease","volume":"29","author":"Pyka","year":"2024","journal-title":"Drug Discov. Today"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.nbd.2012.10.011","article-title":"Mitochondrial dysfunction and oxidative stress in Parkinson\u2019s disease and monogenic parkinsonism","volume":"51","author":"Hauser","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"134296","DOI":"10.1016\/j.neulet.2019.134296","article-title":"Oxidative stress and Parkinson\u2019s disease: Conflict of oxidant-antioxidant systems","volume":"709","author":"Saedi","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/0014-5793(73)80755-0","article-title":"Glutathione peroxidase: A selenoenzyme","volume":"32","author":"Flohe","year":"1973","journal-title":"FEBS Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1089\/ars.2007.1528","article-title":"From selenium to selenoproteins: Synthesis, identity, and their role in human health","volume":"9","author":"Papp","year":"2007","journal-title":"Antioxid. Redox Signal"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"108043","DOI":"10.1016\/j.cclet.2022.108043","article-title":"Selenium and human nervous system","volume":"34","author":"Ding","year":"2023","journal-title":"Chin. Chem. Lett."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1007\/s11427-023-2621-7","article-title":"Selenium metabolism and selenoproteins function in brain and encephalopathy","volume":"68","author":"Li","year":"2025","journal-title":"Sci. China-Life Sci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Zhou, J., Zhang, W., Cao, Z., Lian, S., Li, J., Nie, J., Huang, Y., Zhao, K., He, J., and Liu, C. (2023). Association of Selenium Levels with Neurodegenerative Disease: A Systemic Review and Meta-Analysis. Nutrients, 15.","DOI":"10.21203\/rs.3.rs-2584949\/v1"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e37919","DOI":"10.1097\/MD.0000000000037919","article-title":"Association between Parkinson disease and selenium levels in the body: A systematic review and meta-analysis","volume":"103","author":"Chen","year":"2024","journal-title":"Medicine"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Sun, C.C., Du, Z.R., Liu, X., Yang, Y., Zhou, S.N., Li, C., Cao, X., Zhao, Q., Wong, K.H., and Chen, W.F. (2023). Selenium Forms and Dosages Determined Their Biological Actions in Mouse Models of Parkinson\u2019s Disease. Nutrients, 15.","DOI":"10.3390\/nu15010011"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1016\/j.bbagen.2009.03.026","article-title":"Selenoprotein P-expression, functions, and roles in mammals","volume":"1790","author":"Burk","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1002\/biof.5520140115","article-title":"Plasma selenium in specific and non-specific forms","volume":"14","author":"Burk","year":"2001","journal-title":"Biofactors"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Shi, L., Qian, Q.H., Xie, J.D., Yang, T.S., Zhao, X.Y., Meng, X.Q., Dai, J.G., and Jin, Q.G. (2025). Microglial pyroptosis as a therapeutic target after traumatic spinal cord injury: Current progress and future directions. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1649790"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1089\/ars.2024.0618","article-title":"GPx3 Promotes Functional Recovery after Spinal Cord Injury by Inhibiting Microglial Pyroptosis Through IRAK4\/ROS\/NLRP3 Axis","volume":"42","author":"Liu","year":"2025","journal-title":"Antioxid. Redox Signal."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"100111","DOI":"10.1016\/j.xcrp.2020.100111","article-title":"Selenium-Containing Nanomaterials for Cancer Treatment","volume":"1","author":"Li","year":"2020","journal-title":"Cell Rep. Phys. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1017\/S0007114512004412","article-title":"An in vitro investigation of species-dependent intestinal transport of selenium and the impact of this process on selenium bioavailability","volume":"109","author":"Thiry","year":"2013","journal-title":"Br. J. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1039\/C3MT00185G","article-title":"Selenium biochemistry and its role for human health","volume":"6","author":"Roman","year":"2014","journal-title":"Metallomics"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6655","DOI":"10.1007\/s12035-024-04253-x","article-title":"Selenium Nanoparticles as Neuroprotective Agents: Insights into Molecular Mechanisms for Parkinson\u2019s Disease Treatment","volume":"62","author":"Umapathy","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"117764","DOI":"10.1016\/j.foodres.2025.117764","article-title":"Screening, synthesis and anti-fatigue function verification of selenopeptides","volume":"222","author":"Shi","year":"2025","journal-title":"Food Res. Int."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Garc\u00eda, G., Dublan-Garc\u00eda, O., Arizmendi-Cotero, D., and Oliv\u00e1n, L.M.G. (2022). Antioxidant and Antimicrobial Peptides Derived from Food Proteins. Molecules, 27.","DOI":"10.3390\/molecules27041343"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"24501","DOI":"10.1021\/acs.jafc.5c08197","article-title":"Selenium-Containing Peptides from Foodstuff: Preparation, Bioavailability, Bioactivities, and Future Perspectives","volume":"73","author":"Gu","year":"2025","journal-title":"J. Agric. Food Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"15061","DOI":"10.1021\/acs.jafc.0c05594","article-title":"Selenium-Containing Proteins\/Peptides from Plants: A Review on the Structures and Functions","volume":"68","author":"Zhang","year":"2020","journal-title":"J. Agric. Food Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/j.cell.2008.01.030","article-title":"Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans","volume":"132","author":"Tullet","year":"2008","journal-title":"Cell"},{"key":"ref_26","unstructured":"(2017). National Food Safety Standard-Determination of Selenium in Foods (Standard No. GB 5009.93-2017)."},{"key":"ref_27","unstructured":"(2016). National Food Safety Standard-Determination of Amino Acids in Foods (Standard No. GB 5009.124-2016)."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6206","DOI":"10.1002\/fsn3.4325","article-title":"Separation and purification of antioxidant peptides from Idesia polycarpa Maxim. Cake meal and study of conformational relationship between them","volume":"12","author":"Dou","year":"2024","journal-title":"Food Sci. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"101789","DOI":"10.1016\/j.fochx.2024.101789","article-title":"Characterization, in vitro antioxidant activity and stability of cattle bone collagen peptides-selenium chelate","volume":"23","author":"Li","year":"2024","journal-title":"Food Chem. X"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Offenburger, S.L., Ho, X.Y., Tachie-Menson, T., Coakley, S., Hilliard, M.A., and Gartner, A. (2018). 6-OHDA-induced dopaminergic neurodegeneration in Caenorhabditis elegans is promoted by the engulfment pathway and inhibited by the transthyretin-related protein TTR-33. PLoS Genet., 14.","DOI":"10.1371\/journal.pgen.1007125"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.freeradbiomed.2018.02.030","article-title":"Selenium, selenoprotein P, and Alzheimer\u2019s disease: Is there a link?","volume":"127","author":"Solovyev","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/S1474-4422(19)30024-9","article-title":"CSF and blood biomarkers for Parkinson\u2019s disease","volume":"18","author":"Parnetti","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"109039","DOI":"10.1016\/j.foodhyd.2023.109039","article-title":"Preparation, characterization and functional properties of ternary composite nanoparticles for enhanced water solubility and bioaccessibility of lutein","volume":"144","author":"Du","year":"2023","journal-title":"Food Hydrocoll."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"137398","DOI":"10.1016\/j.foodchem.2023.137398","article-title":"Structure characterization and antioxidant activity of abalone visceral peptides-selenium in vitro","volume":"433","author":"Jia","year":"2024","journal-title":"Food Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1093\/hmg\/9.6.869","article-title":"A role for Caenorhabditis elegans in understanding the function and interactions of human disease genes","volume":"9","author":"Culetto","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1111\/gtc.12175","article-title":"Deletion of the four phospholipid hydroperoxide glutathione peroxidase genes accelerates aging in Caenorhabditis elegans","volume":"19","author":"Sakamoto","year":"2014","journal-title":"Genes Cells"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1016\/S0140-6736(11)61452-9","article-title":"Selenium and human health","volume":"379","author":"Rayman","year":"2012","journal-title":"Lancet"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.abb.2013.02.021","article-title":"Selenium homeostasis and antioxidant selenoproteins in brain: Implications for disorders in the central nervous system","volume":"536","author":"Steinbrenner","year":"2013","journal-title":"Arch. Biochem Biophys."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1046\/j.1471-4159.2003.01531.x","article-title":"Dose-dependent protective effect of selenium in rat model of Parkinson\u2019s disease: Neurobehavioral and neurochemical evidences","volume":"84","author":"Zafar","year":"2003","journal-title":"J. Neurochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1146\/annurev-nutr-071714-034250","article-title":"Regulation of Selenium Metabolism and Transport","volume":"35","author":"Burk","year":"2015","journal-title":"Annu. Rev. Nutr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"115025","DOI":"10.1016\/j.celrep.2024.115025","article-title":"Selenoprotein P is a target for regulating extracellular vesicle biogenesis and secretion from activated microglia in vivo","volume":"43","author":"Ruan","year":"2024","journal-title":"Cell Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3579","DOI":"10.1096\/fj.14-252874","article-title":"Selenoprotein P and apolipoprotein E receptor-2 interact at the blood-brain barrier and also within the brain to maintain an essential selenium pool that protects against neurodegeneration","volume":"28","author":"Burk","year":"2014","journal-title":"FASEB J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.tjnut.2025.01.014","article-title":"Advances of Selenium in Poultry Nutrition and Health","volume":"155","author":"Xu","year":"2025","journal-title":"J. Nutr."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Hou, X., Wang, Z.Y., and Peng, M. (2025). Selenium Compounds and Their Bioactivities: Molecular Mechanisms and Prospects for Functional Food and Therapeutic Applications. Plants, 14.","DOI":"10.3390\/plants14172622"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Zakir, S.K., Jawed, B., Esposito, J.E., Kanwal, R., Pulcini, R., Martinotti, R., Ceci, E., Botteghi, M., Gaudio, F., and Toniato, E. (2025). The Role of Peptides in Nutrition: Insights into Metabolic, Musculoskeletal, and Behavioral Health: A Systematic Review. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26136043"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e07283","DOI":"10.1002\/advs.202507283","article-title":"Redox Cascade in Chicken Skeletal Muscle: SELENOT Suppression in Selenium Deficiency Triggers Disulfidptosis via mtROS-NADPH Dysregulation","volume":"12","author":"Liu","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5903","DOI":"10.7150\/thno.97005","article-title":"Selenoprotein S maintains intestinal homeostasis in ulcerative colitis by inhibiting necroptosis of colonic epithelial cells through modulation of macrophage polarization","volume":"14","author":"Yao","year":"2024","journal-title":"Theranostics"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/18\/1628\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T10:05:27Z","timestamp":1788861927000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/18\/1628"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,8]]},"references-count":47,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cells15181628"],"URL":"https:\/\/doi.org\/10.3390\/cells15181628","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,8]]}}}