{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T09:48:43Z","timestamp":1789465723481,"version":"build-2803163510"},"reference-count":58,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010877","name":"Shenzhen Science and Technology Program","doi-asserted-by":"publisher","award":["JCYJ20240813113330039"],"award-info":[{"award-number":["JCYJ20240813113330039"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Innovation Team Project of Guangdong Provincial Department of Education","award":["2024KCXTD012"],"award-info":[{"award-number":["2024KCXTD012"]}]},{"name":"Basic Research Fund in Shenzhen Natural Science Foundation","award":["JCYJ20241202124709013"],"award-info":[{"award-number":["JCYJ20241202124709013"]}]},{"name":"Yunnan (Kunming) He Zhendan Expert Workstation","award":["YSZJGZZ-2021083"],"award-info":[{"award-number":["YSZJGZZ-2021083"]}]},{"name":"Academician He Zhendan Workstation of Yunnan Province","award":["202305AF150139"],"award-info":[{"award-number":["202305AF150139"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Oxidative stress-mediated neuronal injury is critically involved in the pathogenesis of neurodegenerative disorders, including Alzheimer\u2019s disease and Parkinson\u2019s disease. Manganese dioxide (MnO2), owing to its intrinsic reactive oxygen species (ROS)-scavenging capacity, has emerged as a promising neuroprotective candidate; however, the underlying molecular mechanisms remain insufficiently defined. Methods: Bovine serum albumin-templated MnO2 nanoparticles (BSA-MnO2 NPs) were synthesized, and their protective effects were evaluated in H2O2-treated PC12 cells. Results: BSA-MnO2 NPs significantly inhibited H2O2-induced reductions in cell viability, ROS overproduction, and mitochondrial membrane potential disruption. Mechanistically, H2O2 increased both LC3-II and p62 levels, indicating impaired autophagic flux. Activation of autophagy by serum starvation alleviated H2O2-induced injury, whereas chloroquine exacerbated cellular damage and abolished the protective effects of BSA-MnO2 NPs, suggesting that the restoration of autophagy contributes to BSA-MnO2 NPs-mediated neuroprotection. Further analysis showed that BSA-MnO2 NPs enhanced Akt phosphorylation, while LY294002, a PI3K inhibitor, suppressed Akt activation, disrupted autophagy regulation, and eliminated their neuroprotective effects. In contrast, chloroquine did not affect Akt phosphorylation, indicating that PI3K\/Akt signaling acts upstream of autophagy regulation. Conclusions: Collectively, these findings demonstrate that BSA-MnO2 NPs protect PC12 cells against H2O2-induced oxidative injury by restoring autophagy through the PI3K\/Akt signaling pathway, highlighting a potential role of BSA-MnO2 NPs in the treatment of oxidative-stress-related neurodegenerative disorders.<\/jats:p>","DOI":"10.3390\/pharmaceutics18091156","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T08:16:48Z","timestamp":1789460208000},"page":"1156","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Manganese Dioxide Nanoparticles Protect PC12 Cells Against H2O2-Induced Oxidative Stress Injury by Regulating PI3K\/Akt-Mediated Autophagy"],"prefix":"10.3390","volume":"18","author":[{"given":"Weijian","family":"Zeng","sequence":"first","affiliation":[{"name":"College of Pharmacy, Shenzhen Technology University, Shenzhen 518118, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Duanyang","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Tianlong","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Shenzhen Technology University, Shenzhen 518118, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Zhan-Lu","family":"Ma-H\u00f6gemeier","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Shenzhen Technology University, Shenzhen 518118, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Song","family":"Cai","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Bingfeng","family":"Liu","sequence":"additional","affiliation":[{"name":"The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Chao","family":"Song","sequence":"additional","affiliation":[{"name":"Anning First People\u2019s Hospital Affiliated to Kunming University of Science and Technology, Kunming 650302, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Ling","family":"Guo","sequence":"additional","affiliation":[{"name":"Anning First People\u2019s Hospital Affiliated to Kunming University of Science and Technology, Kunming 650302, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"}]},{"given":"Rihong","family":"Zhai","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2566-3519","authenticated-orcid":false,"given":"Xun","family":"Song","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Shenzhen Technology University, Shenzhen 518118, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Zhendan","family":"He","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Shenzhen Technology University, Shenzhen 518118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5658-3896","authenticated-orcid":false,"given":"Yun","family":"Dong","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Shenzhen Technology University, Shenzhen 518118, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5288","DOI":"10.1038\/s41467-020-19115-y","article-title":"Mechanisms of telomerase inhibition by oxidized and therapeutic dNTPs","volume":"11","author":"Sanford","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s13024-024-00774-0","article-title":"Nuclear pore and nucleocytoplasmic transport impairment in oxidative stress-induced neurodegeneration: Relevance to molecular mechanisms in Pathogenesis of Parkinson\u2019s and other related neurodegenerative diseases","volume":"19","author":"Riaz","year":"2024","journal-title":"Mol. Neurodegener."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101619","DOI":"10.1016\/j.arr.2022.101619","article-title":"Oxidative stress: The core pathogenesis and mechanism of Alzheimer\u2019s disease","volume":"77","author":"Bai","year":"2022","journal-title":"Ageing Res. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6449","DOI":"10.1039\/D1SC00153A","article-title":"Multifunctional peptide-assembled micelles for simultaneously reducing amyloid-beta and reactive oxygen species","volume":"12","author":"Lei","year":"2021","journal-title":"Chem. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"105798","DOI":"10.1016\/j.neuint.2024.105798","article-title":"Combating Parkinson\u2019s disease with plant-derived polyphenols: Targeting oxidative stress and neuroinflammation","volume":"178","author":"Gahtani","year":"2024","journal-title":"Neurochem. Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/s41419-020-03355-3","article-title":"The redox language in neurodegenerative diseases: Oxidative post-translational modifications by hydrogen peroxide","volume":"12","author":"Lee","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.cell.2014.12.019","article-title":"Glial lipid droplets and ROS induced by mitochondrial defects promote neurodegeneration","volume":"160","author":"Liu","year":"2015","journal-title":"Cell"},{"key":"ref_8","first-page":"3481758","article-title":"Hydroxy-alpha-sanshool possesses protective potentials on H2O2-stimulated PC12 cells by suppression of oxidative stress-induced apoptosis through regulation of PI3K\/Akt signal pathway","volume":"2020","author":"Li","year":"2020","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8239642","DOI":"10.1155\/2019\/8239642","article-title":"FA-97, a new synthetic caffeic acid phenethyl ester derivative, protects against oxidative stress-mediated neuronal cell apoptosis and scopolamine-induced cognitive impairment by activating Nrf2\/HO-1 signaling","volume":"2019","author":"Wan","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2630","DOI":"10.1021\/acs.jafc.2c00005","article-title":"Walnut-derived peptide enhances mitophagy via JNK-mediated PINK1 activation to reduce oxidative stress in HT-22 cells","volume":"70","author":"Yang","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"ref_11","first-page":"675","article-title":"Oleuropein attenuates hydrogen peroxide-induced autophagic cell death in human adipose-derived stem cells","volume":"499","author":"Ji","year":"2018","journal-title":"Res. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"102322","DOI":"10.1016\/j.tice.2024.102322","article-title":"Neuroprotective mechanism of ribisin A on H2O2-induced PC12 cell injury model","volume":"87","author":"Zhang","year":"2024","journal-title":"Tissue Cell"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Xiong, Y., Zhou, D., Zheng, K., Bi, W., and Dong, Y. (2022). Extracellular ATP binding to P2Y1 receptors prevents glutamate-induced excitotoxicity: Involvement of Erk1\/2 signaling pathway to suppress autophagy. Front. Neurosci., 16.","DOI":"10.3389\/fnins.2022.901688"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3202","DOI":"10.1021\/nn405773r","article-title":"Multifunctional albumin-MnO2 nanoparticles modulate solid tumor microenvironment by attenuating hypoxia, acidosis, vascular endothelial growth factor and enhance radiation response","volume":"8","author":"Prasad","year":"2014","journal-title":"ACS Nano"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"119467","DOI":"10.1016\/j.biomaterials.2019.119467","article-title":"Manganese dioxide nanoparticles protect cartilage from inflammation-induced oxidative stress","volume":"224","author":"Kumar","year":"2019","journal-title":"Biomaterials"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"14283","DOI":"10.1021\/acsnano.9b07598","article-title":"A MnO2 nanoparticle-dotted hydrogel promotes spinal cord repair via regulating reactive oxygen species microenvironment and synergizing with mesenchymal stem cells","volume":"13","author":"Li","year":"2019","journal-title":"ACS Nano"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e2101526","DOI":"10.1002\/advs.202101526","article-title":"Macrophage-disguised manganese dioxide nanoparticles for neuroprotection by reducing oxidative stress and modulating inflammatory microenvironment in acute ischemic stroke","volume":"8","author":"Li","year":"2021","journal-title":"Adv. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Aschner, M., Skalny, A.V., Notova, S.V., Tinkova, M.N., Lu, R., Skalny, A.A., Santamaria, A., Zhou, J.-C., and Tinkov, A.A. (2026). Molecular mechanisms of manganese oxide nanoparticles toxicity in brain and other tissues: An overview. Front. Biosci., 31.","DOI":"10.31083\/FBL47103"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e00124","DOI":"10.1002\/adtp.202500124","article-title":"Rewiring neuroimmunity: Nanoplatform innovations for CNS disease therapy","volume":"8","author":"Akbar","year":"2025","journal-title":"Adv. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1186\/s12951-025-03750-y","article-title":"Tailored brain metastatic tumor cells-derived apoptotic bodies ameliorate Alzheimer\u2019s disease by promoting microglia efferocytosis and neuroinflammation mitigation","volume":"23","author":"Mu","year":"2025","journal-title":"J. Nanobiotechnol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"110354","DOI":"10.1016\/j.celrep.2022.110354","article-title":"K48\/K63-linked polyubiquitination of ATG9A by TRAF6 E3 ligase regulates oxidative stress-induced autophagy","volume":"38","author":"Wang","year":"2022","journal-title":"Cell Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1080\/15548627.2025.2457910","article-title":"Visualizing bulk autophagy in vivo by tagging endogenous LC3B","volume":"21","author":"Gao","year":"2025","journal-title":"Autophagy"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4784","DOI":"10.1039\/C9TB00546C","article-title":"Development of an interactive tumor vascular suppression strategy to inhibit multidrug resistance and metastasis with pH\/H2O2 responsive and oxygen-producing nanohybrids","volume":"7","author":"Du","year":"2019","journal-title":"J. Mater. Chem. B"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3485","DOI":"10.1016\/j.molcel.2023.09.004","article-title":"S-acylation of p62 promotes p62 droplet recruitment into autophagosomes in mammalian autophagy","volume":"83","author":"Huang","year":"2023","journal-title":"Mol. Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.apsb.2024.10.004","article-title":"Oxidative stress and inflammation in the pathogenesis of neurological disorders: Mechanisms and implications","volume":"15","author":"Dash","year":"2025","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"102667","DOI":"10.1016\/j.arr.2025.102667","article-title":"Oxidative stress and mitochondrial impairment: Key drivers in neurodegenerative disorders","volume":"104","author":"Wen","year":"2025","journal-title":"Ageing Res. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"104961","DOI":"10.1016\/j.neubiorev.2022.104961","article-title":"Mitochondrial dysfunctions, oxidative stress and neuroinflammation as therapeutic targets for neurodegenerative diseases: An update on current advances and impediments","volume":"144","author":"Rehman","year":"2023","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.biopha.2015.07.025","article-title":"Oxidative stress, mitochondrial dysfunction and neurodegenerative diseases; a mechanistic insight","volume":"74","author":"Bhat","year":"2015","journal-title":"Biomed. Pharmacother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1007\/s10571-015-0235-1","article-title":"Propofol protects against H2O2-induced oxidative injury in differentiated PC12 cells via inhibition of Ca2+-dependent NADPH oxidase","volume":"36","author":"Chen","year":"2016","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"104795","DOI":"10.1016\/j.tiv.2020.104795","article-title":"Cr(VI) induces ROS-mediated mitochondrial-dependent apoptosis in neuronal cells via the activation of Akt\/ERK\/AMPK signaling pathway","volume":"65","author":"Fu","year":"2020","journal-title":"Toxicol. In Vitro"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"103940","DOI":"10.1016\/j.redox.2025.103940","article-title":"Endogenous mitochondrial hydrogen peroxide regulates neurogenesis during cortical development","volume":"88","author":"Mengual","year":"2025","journal-title":"Redox. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Petricca, S., Matrone, A., Capece, D., Flati, I., Flati, V., Ricevuto, E., Celenza, G., Franceschini, N., Mastrangelo, M., and Pellegrini, C. (2025). Pyrroloquinoline quinone (PQQ) attenuates hydrogen peroxide-induced injury through the enhancement of mitochondrial function in human trabecular meshwork cells. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26146938"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ejphar.2016.05.033","article-title":"Inhibitory effects of tyrphostin AG-related compounds on oxidative stress-sensitive transient receptor potential channel activation","volume":"786","author":"Toda","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/s41586-020-2032-3","article-title":"Hydrogen peroxide sensor HPCA1 is an LRR receptor kinase in Arabidopsis","volume":"578","author":"Wu","year":"2020","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"104027","DOI":"10.1016\/j.redox.2026.104027","article-title":"NMDAR and glutamate control axon growth by regulating Rac1-dependent actin dynamics and H2O2 production","volume":"90","author":"Villablanca","year":"2026","journal-title":"Redox. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Li, J., Li, Y., Liu, Y., Yu, H., Xu, N., Huang, D., Xue, Y., Li, S., Chen, H., and Liu, J. (2021). Fibroblast growth factor 21 ameliorates NaV1.5 and Kir2.1 channel dysregulation in human AC16 cardiomyocytes. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.715466"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.conb.2018.02.008","article-title":"Neuronal autophagy and intercellular regulation of homeostasis in the brain","volume":"51","author":"Kulkarni","year":"2018","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1146\/annurev-cellbio-100818-125242","article-title":"Autophagy in Neurons","volume":"35","author":"Stavoe","year":"2019","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1007\/s12035-013-8457-z","article-title":"Autophagy modulation for Alzheimer\u2019s disease therapy","volume":"48","author":"Zhu","year":"2013","journal-title":"Mol. Neurobiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s10571-016-0386-8","article-title":"Autophagy and Alzheimer\u2019s disease","volume":"37","author":"Li","year":"2017","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/978-981-15-4272-5_2","article-title":"Autophagy and Parkinson\u2019s disease","volume":"1207","author":"Lu","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1038\/s43587-026-01108-z","article-title":"Reduced ULK1 links impaired autophagy and mitophagy to Alzheimer\u2019s disease pathology","volume":"6","author":"Pan","year":"2026","journal-title":"Nat. Aging"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"118364","DOI":"10.1016\/j.ecoenv.2025.118364","article-title":"Characterizing microglial heterogeneity in autophagy impairment of Paraquat-induced Parkinson\u2019s disease-like neurodegeneration","volume":"299","author":"Zhang","year":"2025","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1080\/15548627.2016.1247143","article-title":"Autophagy impairment with lysosomal and mitochondrial dysfunction is an important characteristic of oxidative stress-induced senescence","volume":"13","author":"Tai","year":"2017","journal-title":"Autophagy"},{"key":"ref_45","first-page":"1827","article-title":"N-linoleyltyrosine protects PC12 cells against oxidative damage via autophagy: Possible involvement of CB1 receptor regulation","volume":"46","author":"Liu","year":"2020","journal-title":"Int. J. Mol. Med."},{"key":"ref_46","first-page":"6","article-title":"Apocynum venetum leaf extract protects against H2O2-induced oxidative stress by increasing autophagy in PC12 cells","volume":"13","author":"Feng","year":"2020","journal-title":"Biomed. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1111\/jnc.15002","article-title":"Autophagy in neurodegeneration: New insights underpinning therapy for neurological diseases","volume":"154","author":"Corti","year":"2020","journal-title":"J. Neurochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"17982","DOI":"10.1039\/D0NR04067C","article-title":"Nanostructured manganese dioxide for anticancer applications: Preparation, diagnosis, and therapy","volume":"12","author":"Zhang","year":"2020","journal-title":"Nanoscale"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1021\/acsbiomaterials.1c01286","article-title":"Multienzymatic antioxidant activity of manganese-based nanoparticles for protection against oxidative cell damage","volume":"8","author":"Zhang","year":"2022","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.ejphar.2009.04.066","article-title":"Effects of H2O2 at rat myenteric neurones in culture","volume":"615","author":"Pouokam","year":"2009","journal-title":"Eur. J. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Huang, Y., Ruan, Y., Ma, Y., Chen, D., Zhang, T., Fan, S., Lin, W., Huang, Y., Lu, H., and Xu, J.-F. (2023). Immunomodulatory activity of manganese dioxide nanoparticles: Promising for novel vaccines and immunotherapeutics. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1128840"},{"key":"ref_52","first-page":"445","article-title":"Manganese and calcium transport in mitochondria: Implications for manganese toxicity","volume":"20","author":"Gavin","year":"1999","journal-title":"Neurotoxicology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1002\/bab.2104","article-title":"The interplay of ROS and the PI3K\/Akt pathway in autophagy regulation","volume":"69","author":"Kma","year":"2022","journal-title":"Biotechnol. Appl. Biochem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"111772","DOI":"10.1016\/j.yexcr.2019.111772","article-title":"Sodium butyrate causes alpha-synuclein degradation by an Atg5-dependent and PI3K\/Akt\/mTOR-related autophagy pathway","volume":"387","author":"Qiao","year":"2020","journal-title":"Exp. Cell Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.fct.2018.12.003","article-title":"Apios americana Medik flowers extract protects PC12 cells against H2O2 induced neurotoxicity via regulating autophagy","volume":"124","author":"Chu","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"9549175","DOI":"10.1155\/cdr\/9549175","article-title":"Astragaloside IV alleviates H2O2-induced mitochondrial dysfunction and inhibits mitophagy via PI3K\/AKT\/mTOR pathway","volume":"2025","author":"Qi","year":"2025","journal-title":"Cardiovasc. Ther."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e22461","DOI":"10.1002\/jbt.22461","article-title":"Repression of Kisspeptin1 weakens hydrogen peroxide-caused injury in HTR8 cells via adjusting PI3K\/AKT\/mTOR pathway","volume":"34","author":"Han","year":"2020","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3892\/ijmm.2025.5548","article-title":"Gossypin induces apoptosis and autophagy via the MAPK\/JNK pathway in HT-29 human colorectal cancer cells","volume":"56","author":"Moon","year":"2025","journal-title":"Int. J. Mol. Med."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/9\/1156\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T08:26:58Z","timestamp":1789460818000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/9\/1156"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":58,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["pharmaceutics18091156"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics18091156","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]}}}