{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:14:01Z","timestamp":1790115241604,"version":"4.0.1"},"reference-count":30,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T00:00:00Z","timestamp":1737417600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"2023 General Undergraduate College Scientific Research Project (Youth Project) of Guizhou Education Department","award":["QJJ-2022246"],"award-info":[{"award-number":["QJJ-2022246"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>This study investigates the protective properties of melatonin in an <jats:italic>in vivo<\/jats:italic> Parkinson\u2019s disease (PD) model, focusing on the underlying mechanisms involving heat shock proteins (HSPs).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Twelve adult male C57BL\/6 mice were randomly divided into four groups (normal control, melatonin control, Parkinson\u2019s model, and melatonin treatment; <jats:italic>n<\/jats:italic> = 3 per group) and housed in a single cage. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was injected intraperitoneally in the Parkinson\u2019s model and treatment groups to establish a subacute PD model, while controls received saline. Limb motor ability was assessed 1 h after the final injection using behavioral tests, including the open field test to evaluate central zone entries and average movement. Dopamine transporter (DAT) expression in the striatum was analyzed by immunohistochemistry, and Western blot was used to measure autophagy proteins and HSP70 levels.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>The PD mouse model was successfully established through MPTP stimulation. Compared to the normal control group, the model group showed a significant reduction in the frequency of entering the central zone and average movement. The number of DAT-positive cells in the brain also decreased significantly. The expression levels of HSP70 and CDK5 were significantly lower, while the expression levels of LC3 II \/LC3I and p62 increased significantly. In the MT treatment group, both the frequency of entering the central zone and the average movement were significantly higher compared to the model group. DAT-positive cells in the midbrain also increased significantly. The expression levels of HSP70 and CDK5 were significantly elevated, while the expression levels of LC3 II \/LC3I and p62 protein were significantly decreased.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Melatonin exerts a protective effect against MPP<jats:sup>+<\/jats:sup>-induced damage to dopaminergic neurons, presumably by upregulating HSP70, which inhibits neuronal autophagy.<\/jats:p>\n<\/jats:sec>","DOI":"10.7717\/peerj.18788","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T08:25:51Z","timestamp":1737447951000},"page":"e18788","source":"Crossref","is-referenced-by-count":4,"title":["Melatonin attenuates MPP<sup>+<\/sup>-induced autophagy <i>via<\/i> heat shock protein in the Parkinson\u2019s disease mouse model"],"prefix":"10.7717","volume":"13","author":[{"given":"Yinli","family":"Guo","sequence":"first","affiliation":[{"name":"Institute of Innovation and Entrepreneurship, Guizhou Education University, Guizhou, Wudang District, Guiyang City, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengbo","family":"Liu","sequence":"additional","affiliation":[{"name":"Medical section, Jiang Ling County People\u2019s Hospital, Hubei, Jiangling County, Jingzhou City, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4443","published-online":{"date-parts":[[2025,1,21]]},"reference":[{"issue":"16","key":"10.7717\/peerj.18788\/ref-1","doi-asserted-by":"publisher","first-page":"9090","DOI":"10.3390\/ijms25169090","article-title":"Hsp70 negatively regulates autophagy via governing AMPK activation, and dual Hsp70-autophagy inhibition induces synergetic cell death in NSCLC Cells","volume":"25","author":"Alhasan","year":"2024","journal-title":"International Journal of Molecular Sciences"},{"issue":"7","key":"10.7717\/peerj.18788\/ref-2","doi-asserted-by":"publisher","first-page":"8417","DOI":"10.1021\/acsami.3c17092","article-title":"Melatonin-loaded nanoparticles augment mitophagy to retard parkinson\u2019s disease","volume":"16","author":"Biswal","year":"2024","journal-title":"ACS Applied Materials & Interfaces"},{"issue":"1","key":"10.7717\/peerj.18788\/ref-3","doi-asserted-by":"publisher","first-page":"105065","DOI":"10.1016\/j.phrs.2020.105065","article-title":"Preventive treatments to slow substantia nigra damage and Parkinson\u2019s disease progression: a critical perspective review","volume":"161","author":"Bj\u00f8rklund","year":"2020","journal-title":"Pharmacological Research"},{"issue":"10291","key":"10.7717\/peerj.18788\/ref-4","doi-asserted-by":"publisher","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"},{"issue":"2","key":"10.7717\/peerj.18788\/ref-5","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1007\/s11065-022-09540-9","article-title":"Deep brain stimulation in parkinson disease: a meta-analysis of the long-term neuropsychological outcomes","volume":"33","author":"Bucur","year":"2023","journal-title":"Neuropsychology Review"},{"issue":"3","key":"10.7717\/peerj.18788\/ref-6","doi-asserted-by":"publisher","first-page":"a024091","DOI":"10.1101\/cshperspect.a024091","article-title":"Cell biology and pathophysiology of \u03b1-synuclein","volume":"8","author":"Burr\u00e9","year":"2018","journal-title":"Cold Spring Harbor Perspectives in Medicine"},{"issue":"2","key":"10.7717\/peerj.18788\/ref-7","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1111\/jpi.12343","article-title":"Melatonin prevents the dynamin-related protein 1-dependent mitochondrial fission and oxidative insult in the cortical neurons after 1-methyl-4-phenylpyridinium treatment","volume":"61","author":"Chuang","year":"2016","journal-title":"Journal of Pineal Research"},{"issue":"1","key":"10.7717\/peerj.18788\/ref-8","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1001\/jamaneurol.2017.3299","article-title":"The parkinson pandemic-A call to action","volume":"75","author":"Dorsey","year":"2018","journal-title":"JAMA Neurology"},{"key":"10.7717\/peerj.18788\/ref-9","doi-asserted-by":"publisher","first-page":"612","DOI":"10.3389\/fnins.2018.00612","article-title":"Parkinson\u2019s disease: biomarkers, treatment, and risk factors","volume":"12","author":"Emamzadeh","year":"2018","journal-title":"Frontiers in Neuroscience"},{"issue":"2","key":"10.7717\/peerj.18788\/ref-10","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1039\/c2mt20164j","article-title":"Metallobiology of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity","volume":"5","author":"Hare","year":"2013","journal-title":"Metallomics"},{"key":"10.7717\/peerj.18788\/ref-11","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.bbrc.2022.06.099","article-title":"Melatonin attenuates MPP(+)-induced apoptosis via heat shock protein in a Parkinson\u2019s disease model","volume":"621","author":"Jung","year":"2022","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"10.7717\/peerj.18788\/ref-12","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3389\/fnagi.2018.00012","article-title":"Microglia polarization, gene-environment interactions and Wnt\/\u03b2-catenin signaling: emerging roles of glia-neuron and Glia-Stem\/Neuroprogenitor crosstalk for dopaminergic neurorestoration in aged parkinsonian brain","volume":"10","author":"L\u2019Episcopo","year":"2018","journal-title":"Frontiers in Aging Neuroscience"},{"issue":"10","key":"10.7717\/peerj.18788\/ref-13","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1016\/j.tins.2023.07.005","article-title":"The systemic immune response in Parkinson\u2019s disease: focus on the peripheral immune component","volume":"46","author":"Lauritsen","year":"2023","journal-title":"Trends in Neurosciences"},{"issue":"3","key":"10.7717\/peerj.18788\/ref-14","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1007\/s00415-016-8370-2","article-title":"MDS clinical diagnostic criteria for Parkinson\u2019s disease in China","volume":"264","author":"Li","year":"2017","journal-title":"Journal of Neurology"},{"issue":"2016","key":"10.7717\/peerj.18788\/ref-15","doi-asserted-by":"publisher","first-page":"116747","DOI":"10.1016\/j.lfs.2019.116747","article-title":"Neuroprotective effects of increasing levels of HSP70 against neuroinflammation in Parkinson\u2019s disease model by inhibition of NF-\u03baB and STAT3","volume":"234","author":"Li","year":"2019","journal-title":"Life Sciences"},{"issue":"10","key":"10.7717\/peerj.18788\/ref-16","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1038\/s41419-023-06154-8","article-title":"Autophagy: regulator of cell death","volume":"14","author":"Liu","year":"2023","journal-title":"Cell Death & Disease"},{"issue":"4","key":"10.7717\/peerj.18788\/ref-17","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1016\/j.cell.2011.10.026","article-title":"Autophagy: renovation of cells and tissues","volume":"147","author":"Mizushima","year":"2011","journal-title":"Cell"},{"key":"10.7717\/peerj.18788\/ref-18","doi-asserted-by":"publisher","first-page":"383","DOI":"10.7554\/eLife.30760","article-title":"Stress-induced Cdk5 activity enhances cytoprotective basal autophagy in Drosophila melanogaster by phosphorylating acinus at serine(437)","volume":"6","author":"Nandi","year":"2017","journal-title":"Elife"},{"issue":"10","key":"10.7717\/peerj.18788\/ref-19","doi-asserted-by":"publisher","first-page":"1435","DOI":"10.3390\/biom13101435","article-title":"Autophagy in Parkinson\u2019s disease","volume":"13","author":"Nechushtai","year":"2023","journal-title":"Biomolecules"},{"issue":"3","key":"10.7717\/peerj.18788\/ref-20","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1007\/s12640-012-9337-4","article-title":"Melatonin antioxidative defense: therapeutical implications for aging and neurodegenerative processes","volume":"23","author":"Pandi-Perumal","year":"2013","journal-title":"Neurotoxicity Research"},{"issue":"2","key":"10.7717\/peerj.18788\/ref-21","doi-asserted-by":"publisher","first-page":"102456","DOI":"10.1016\/j.jtherbio.2019.102456","article-title":"Role of melatonin and HSF-1\\HSP-70 in modulating cold stress-induced immunosuppression in a tropical rodent- Funambulus pennanti","volume":"87","author":"Rastogi","year":"2020","journal-title":"Journal of Thermal Biology"},{"issue":"3","key":"10.7717\/peerj.18788\/ref-22","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.lfs.2019.03.057","article-title":"Parkinson\u2019s disease: mechanisms, translational models and management strategies","volume":"226","author":"Raza","year":"2019","journal-title":"Life Sciences"},{"issue":"2","key":"10.7717\/peerj.18788\/ref-23","doi-asserted-by":"publisher","first-page":"246","DOI":"10.4103\/1673-5374.317958","article-title":"Dying by fire: noncanonical functions of autophagy proteins in neuroinflammation and neurodegeneration","volume":"17","author":"Rickman","year":"2022","journal-title":"Neural Regeneration Research"},{"issue":"1","key":"10.7717\/peerj.18788\/ref-24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.cger.2019.08.002","article-title":"Parkinson disease epidemiology, pathology, genetics, and pathophysiology","volume":"36","author":"Simon","year":"2020","journal-title":"Clinics in Geriatric Medicine"},{"issue":"1","key":"10.7717\/peerj.18788\/ref-25","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/s11658-023-00458-5","article-title":"Hsp70-Bim interaction facilitates mitophagy by recruiting parkin and TOMM20 into a complex","volume":"28","author":"Song","year":"2023","journal-title":"Cellular & Molecular Biology Letters"},{"issue":"2","key":"10.7717\/peerj.18788\/ref-26","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/S0006-8993(00)02341-6","article-title":"Discrimination between changes in glucocorticoid receptor expression and activation in rat brain using western blot analysis","volume":"868","author":"Spencer","year":"2000","journal-title":"Brain Research"},{"issue":"10","key":"10.7717\/peerj.18788\/ref-27","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1080\/15548627.2015.1082020","article-title":"Melatonin attenuates MPTP-induced neurotoxicity via preventing CDK5-mediated autophagy and SNCA\/\u03b1-synuclein aggregation","volume":"11","author":"Su","year":"2015","journal-title":"Autophagy"},{"issue":"4","key":"10.7717\/peerj.18788\/ref-28","doi-asserted-by":"publisher","first-page":"E734","DOI":"10.1152\/ajpendo.00071.2020","article-title":"IGF-1 inhibits MPTP\/MPP(+)-induced autophagy on dopaminergic neurons through the IGF-1R\/PI3K-Akt-mTOR pathway and GPER","volume":"319","author":"Wang","year":"2020","journal-title":"American Journal of Physiology-Endocrinology and Metabolism"},{"key":"10.7717\/peerj.18788\/ref-29","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1007\/978-3-319-51409-3","article-title":"The role of Hsp70 in the regulation of autophagy in gametogenesis, pregnancy, and parturition","volume":"222","author":"Witkin","year":"2017","journal-title":"Advances in Anatomy, Embryology and Cell Biology"},{"issue":"2","key":"10.7717\/peerj.18788\/ref-30","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.arr.2016.05.008","article-title":"Can \u2018calpain-cathepsin hypothesis\u2019 explain Alzheimer neuronal death?","volume":"32","author":"Yamashima","year":"2016","journal-title":"Ageing Research Reviews"}],"container-title":["PeerJ"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/peerj.com\/articles\/18788.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/18788.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/18788.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/18788.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T08:25:57Z","timestamp":1737447957000},"score":1,"resource":{"primary":{"URL":"https:\/\/peerj.com\/articles\/18788"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,21]]},"references-count":30,"alternative-id":["10.7717\/peerj.18788"],"URL":"https:\/\/doi.org\/10.7717\/peerj.18788","archive":["CLOCKSS","LOCKSS","Portico"],"relation":{},"ISSN":["2167-8359"],"issn-type":[{"value":"2167-8359","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,21]]},"article-number":"e18788"}}