{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T05:30:50Z","timestamp":1777527050957,"version":"3.51.4"},"reference-count":64,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Malaga","award":["PAIDI-CTS156"],"award-info":[{"award-number":["PAIDI-CTS156"]}]},{"name":"University of Malaga","award":["PAIDI-CTS 655"],"award-info":[{"award-number":["PAIDI-CTS 655"]}]},{"name":"Campus de Excelencia Internacional Andaluc\u00eda Tech","award":["PAIDI-CTS156"],"award-info":[{"award-number":["PAIDI-CTS156"]}]},{"name":"Campus de Excelencia Internacional Andaluc\u00eda Tech","award":["PAIDI-CTS 655"],"award-info":[{"award-number":["PAIDI-CTS 655"]}]},{"name":"Andalusian Government","award":["PAIDI-CTS156"],"award-info":[{"award-number":["PAIDI-CTS156"]}]},{"name":"Andalusian Government","award":["PAIDI-CTS 655"],"award-info":[{"award-number":["PAIDI-CTS 655"]}]},{"name":"Sponsorship Chair for Advanced Neurosurgery, University of Malaga","award":["PAIDI-CTS156"],"award-info":[{"award-number":["PAIDI-CTS156"]}]},{"name":"Sponsorship Chair for Advanced Neurosurgery, University of Malaga","award":["PAIDI-CTS 655"],"award-info":[{"award-number":["PAIDI-CTS 655"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In this study, we explore the neuroprotective and modulatory potential of graphenic materials (GMs) in terms of the maturation of dopaminergic neurons and their capacity to counteract the cellular stress induced by toxins such as MPP+ (1-methyl-4-phenylpyridinium) and Tunicamycin. We found that GMs promote significant morphological changes in neuronal cells after prolonged exposure, enhancing both differentiation and cellular adhesion. Through structural analysis, we unveiled a complex organization of GMs and a marked upregulation of tyrosine hydroxylase (TH), a key marker of mature dopaminergic neurons. Under oxidative stress induced by MPP+, GMs significantly reduced the release of lactate dehydrogenase (LDH), indicating protection against mitochondrial damage. Moreover, GMs substantially decreased the levels of \u03b1-synuclein (\u03b1-Syn), a protein closely associated with neurodegenerative disorders such as Parkinson\u2019s disease. Notably, partially reduced graphene oxide (PRGO) and fully reduced graphene oxide (FRGO) films were particularly effective at reducing \u03b1-Syn-associated toxicity compared to positive controls. Under conditions of endoplasmic reticulum (ER) stress triggered by Tunicamycin, GMs\u2014especially PRGO microflakes\u2014modulated the unfolded protein response (UPR) pathway. This effect was evidenced by the increased expression of BIP\/GRP78 and the decreased phosphorylation of stress sensors such as PERK and eIF2\u03b1; this suggests that a protective role is played against ER stress. Additionally, GMs enhanced the synthesis of Torsin 1A, a chaperone protein involved in correcting protein folding defects, with PRGO microflakes showing up to a fivefold increase relative to the controls. Through the cFos analysis, we further revealed a pre-adaptive cellular response in GM-treated cells exposed to MPP+, with PRGO microflakes inducing a significant twofold increase in cFos expression compared to the positive control, indicating partial protection against oxidative stress. In conclusion, these results underscore GMs\u2019 capacity to modulate the critical cellular pathways involved in oxidative, mitochondrial, and ER stress responses, positioning them as promising candidates for future neuroprotective and therapeutic strategies.<\/jats:p>","DOI":"10.3390\/ijms26188821","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T14:14:55Z","timestamp":1757513695000},"page":"8821","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Neuroprotective Effects of Low-Dose Graphenic Materials on SN4741 Embryonic Stem Cells Against ER Stress and MPTP-Induced Oxidative Stress"],"prefix":"10.3390","volume":"26","author":[{"given":"David","family":"Vallejo Perez","sequence":"first","affiliation":[{"name":"Neurosurgery Unit, Biomedicine Research Institute of Malaga (IBIMA), Department of Neurosurgery, M\u00e1laga Regional University Hospital, 29010 Malaga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8393-6623","authenticated-orcid":false,"given":"Monica","family":"Navarro","sequence":"additional","affiliation":[{"name":"Catedra de Fisiologia, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, Buenos Aires 1113, Argentina"},{"name":"Instituto de Qu\u00edmica y Metabolismo del Farmaco (IQUIMEFA), CONICET-Universidad de Buenos Aires, Buenos Aires 1113, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5591-4319","authenticated-orcid":false,"given":"Beatriz","family":"Segura-Segura","sequence":"additional","affiliation":[{"name":"Vaccine Research Department, Fundaci\u00f3n para el Fomento de la Investigaci\u00f3n Sanitaria y Biom\u00e9dica de la Comunidad Valenciana (FISABIO), 46024 Valencia, Spain"},{"name":"CIBER de Epidemiolog\u00eda y Salud Publica, Instituto de Salud P\u00fablica de Valencia, 46024 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rune","family":"Wendelbo","sequence":"additional","affiliation":[{"name":"Shift Materials AS, 0663 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Bandr\u00e9s-Ciga","sequence":"additional","affiliation":[{"name":"Center for Alzheimer\u2019s and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel A.","family":"Arraez","sequence":"additional","affiliation":[{"name":"Neurosurgery Unit, Biomedicine Research Institute of Malaga (IBIMA), Department of Neurosurgery, M\u00e1laga Regional University Hospital, 29010 Malaga, Spain"},{"name":"Department of Surgical Specialties, Biochemistry and Immunology, School of Medicine, University of M\u00e1laga, 29071 Malaga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cinta","family":"Arraez","sequence":"additional","affiliation":[{"name":"Neurosurgery Unit, Biomedicine Research Institute of Malaga (IBIMA), Department of Neurosurgery, M\u00e1laga Regional University Hospital, 29010 Malaga, Spain"},{"name":"Department of Neurosurgery, Vithas Hospital, 29016 Malaga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3629-4883","authenticated-orcid":false,"given":"Noela","family":"Rodriguez-Losada","sequence":"additional","affiliation":[{"name":"Faculty of Science Education, Department of Didactic Science Education, University of Malaga, 29010 Malaga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/nrn.2017.62","article-title":"Non-motor features of Parkinson disease","volume":"18","author":"Schapira","year":"2017","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1159\/000101892","article-title":"Stem-cell-based strategies for the treatment of Parkinson\u2019s disease","volume":"4","author":"Parish","year":"2007","journal-title":"Neurodegener Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/s41531-025-00967-4","article-title":"Insights into ancestral diversity in Parkinson\u2019s disease risk: A comparative assessment of polygenic risk scores","volume":"11","author":"Grant","year":"2025","journal-title":"NPJ Park. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Yang, H.M. (2025). Mitochondrial Dysfunction in Neurodegenerative Diseases. Cells, 14.","DOI":"10.3390\/cells14040276"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s10020-024-00808-9","article-title":"Endoplasmic reticulum stress and therapeutic strategies in metabolic, neurodegenerative diseases and cancer","volume":"30","author":"Yuan","year":"2024","journal-title":"Mol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Su, H.Y., Waldron, R.T., Gong, R., Ramanujan, V.K., Pandol, S.J., and Lugea, A. (2016). The Unfolded Protein Response Plays a Predominant Homeostatic Role in Response to Mitochondrial Stress in Pancreatic Stellate Cells. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0148999"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"110621","DOI":"10.1016\/j.neuropharm.2025.110621","article-title":"Sinapic acid attenuates PERK-dependent ER stress signaling and resolves \u03b1-synuclein pathology in rotenone-induced Parkinson\u2019s disease rat model","volume":"279","author":"Yasser","year":"2025","journal-title":"Neuropharmacology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nrn1683","article-title":"Stress and the brain: From adaptation to disease","volume":"6","author":"Holsboer","year":"2005","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.neuroscience.2017.12.033","article-title":"Exploring the Interaction Between eIF2\u03b1 Dysregulation, Acute Endoplasmic Reticulum Stress and DYT1 Dystonia in the Mammalian Brain","volume":"371","author":"Beauvais","year":"2018","journal-title":"Neuroscience"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"148742","DOI":"10.1016\/j.brainres.2023.148742","article-title":"Endoplasmic reticulum stress and its role in various neurodegenerative diseases","volume":"1826","author":"Singh","year":"2024","journal-title":"Brain Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Li, X., Zhuang, Y., Zhang, Y.R., Fan, K.K., Chen, X.X., Chen, X.X., Liu, X.Y., Sun, J., and Liu, L. (2025). Combined inhibition of dopamine D1\/D2 receptors induces cognitive and emotional dysfunction through oxidative stress and dopaminergic neuron damage. Front. Behav. Neurosci., 19.","DOI":"10.3389\/fnbeh.2025.1621017"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Liu, T., Kong, X., Qiao, J., and Wei, J. (2025). Decoding Parkinson\u2019s Disease: The interplay of cell death pathways, oxidative stress, and therapeutic innovations. Redox Biol., 85.","DOI":"10.1016\/j.redox.2025.103787"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1007\/s00018-011-0850-z","article-title":"Transgenic expression and activation of PGC-1\u03b1 protect dopaminergic neurons in the MPTP mouse model of Parkinson\u2019s disease","volume":"69","author":"Tselykh","year":"2012","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"69","DOI":"10.4103\/1673-5374.374142","article-title":"Lactate metabolism in neurodegenerative diseases","volume":"19","author":"Yang","year":"2024","journal-title":"Neural Regen. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1002\/mds.27864","article-title":"The Genetic Architecture of Parkinson Disease in Spain: Characterizing Population-Specific Risk, Differential Haplotype Structures, and Providing Etiologic Insight","volume":"34","author":"Ahmed","year":"2019","journal-title":"Mov. Disord."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Li, J., Chen, L., Qin, Q., Wang, D., Zhao, J., Gao, H., Yuan, X., Zhang, J., Zou, Y., and Mao, Z. (2022). Upregulated hexokinase 2 expression induces the apoptosis of dopaminergic neurons by promoting lactate production in Parkinson\u2019s disease. Neurobiol. Dis., 163.","DOI":"10.1016\/j.nbd.2021.105605"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.neurobiolaging.2020.02.012","article-title":"Young-onset and late-onset Parkinson\u2019s disease exhibit a different profile of fluid biomarkers and clinical features","volume":"90","author":"Schirinzi","year":"2020","journal-title":"Neurobiol. Aging."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/S0165-0173(98)00018-6","article-title":"Inducible and Constitutive Transcription Factors in the Mammalian Nervous System: Control of Gene Expression by Jun, Fos and Krox, and CREB\/ATF Proteins","volume":"28","author":"Herdegen","year":"1998","journal-title":"Brain Res. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1038\/nn1296","article-title":"Restructuring the neuronal stress response with anti-glucocorticoid gene delivery","volume":"7","author":"Kaufer","year":"2004","journal-title":"Nat. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.neulet.2005.12.021","article-title":"5-HT1A receptor activation counteracts c-Fos immunoreactivity induced in serotonin neurons of the raphe nuclei after immobilization stress in the male rat","volume":"397","author":"Rioja","year":"2006","journal-title":"Neurosci. Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jbior.2016.05.001","article-title":"Gene regulation in the immediate-early response process","volume":"62","author":"Bahrami","year":"2016","journal-title":"Adv. Biol. Regul."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1126\/science.1102896","article-title":"Electric field effect in atomically thin carbon films","volume":"306","author":"Novoselov","year":"2004","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s13770-013-0384-6","article-title":"Culture of neural cells and stem cells on graphene","volume":"10","author":"Ryu","year":"2013","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jare.2020.01.009","article-title":"Overexpression of alpha-synuclein promotes both cell proliferation and cell toxicity in human SH-SY5Y neuroblastoma cells","volume":"23","author":"Larriva","year":"2020","journal-title":"J. Adv. Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Rodriguez-Losada, N., Wendelbob, R., Oca\u00f1a, M.C., Casares, A.D., Guzman de Villor\u00eda, R., Aguirre Gomez, J.A., Arraez, M.A., Gonzalez-Alegre, P., Medina, M.A., and Arenas, E. (2020). Graphene Oxide and Reduced Derivatives, as Powder or Film Scaffolds, Differentially Promote Dopaminergic Neuron Differentiation and Survival. Front. Neurosci., 14.","DOI":"10.3389\/fnins.2020.570409"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Convertino, D., Trincavelli, M.L., Giacomelli, C., Marchetti, L., and Coletti, C. (2023). Graphene-based nanomaterials for peripheral nerve regeneration. Front. Bioeng. Biotechnol., 11.","DOI":"10.3389\/fbioe.2023.1306184"},{"key":"ref_27","first-page":"94","article-title":"In Vitro Evaluation of Biocompatibility of Uncoated Thermally Reduced Graphene and Carbon Nanotube-Loaded PVDF Membranes with Adult Neural Stem Cell-Derived Neurons and Glia","volume":"4","author":"Verdejo","year":"2016","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.brainres.2004.09.005","article-title":"Prevention of endoplasmic reticulum stress-induced cell death by brain-derived neurotrophic factor in cultured cerebral cortical neurons","volume":"1028","author":"Shimoke","year":"2004","journal-title":"Brain Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.neulet.2012.02.027","article-title":"Advances in natural biomaterials for nerve tissue repair","volume":"519","author":"Khaing","year":"2012","journal-title":"Neurosci. Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/s41699-022-00330-8","article-title":"Cytotoxicity survey of commercial graphene materials from worldwide","volume":"6","author":"Malhotra","year":"2022","journal-title":"Npj 2D Mater. Appl."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ikram, R., Shamsuddin, S.A.A., Mohamed Jan, B., Abdul Qadir, M., Kenanakis, G., Stylianakis, M.M., and Anastasiadis, S.H. (2022). Impact of Graphene Derivatives as Artificial Extracellular Matrices on Mesenchymal Stem Cells. Molecules, 27.","DOI":"10.3390\/molecules27020379"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6464","DOI":"10.1039\/D3MA00623A","article-title":"Advances in graphene-based nanoplatforms and their application in Parkinson\u2019s disease","volume":"4","author":"Oz","year":"2023","journal-title":"Mater. Adv."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Farokhi, M., Mottaghitalab, F., Saeb, M.R., Shojaei, S., Zarrin, N.K., Thomas, S., and Ramakrishna, S. (2021). Conductive Biomaterials as Substrates for Neural Stem Cells Differentiation towards Neuronal Lineage Cells. Macromol. Biosci., 21.","DOI":"10.1002\/mabi.202000123"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"\u00c1sgr\u00edmsd\u00f3ttir, E.S., and Arenas, E. (2020). Midbrain Dopaminergic Neuron Development at the Single Cell Level: In vivo and in Stem Cells. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00463"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Ye, T., Yang, Y., Bai, J., Wu, F.Y., Zhang, L., Meng, L.Y., and Lan, Y. (2023). The mechanical, optical, and thermal properties of graphene influencing its pre-clinical use in treating neurological diseases. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1162493"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7022","DOI":"10.1016\/j.biomaterials.2014.04.066","article-title":"Dose ranging, expanded acute toxicity and safety pharmacology studies for intravenously administered functionalized graphene nanoparticle formulations","volume":"35","author":"Kanakia","year":"2014","journal-title":"Biomaterials"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.jare.2024.01.036","article-title":"New molecular mechanisms to explain the neuroprotective effects of insulin-like growth factor II in a cellular model of Parkinson\u2019s disease","volume":"67","author":"Valverde","year":"2025","journal-title":"J. Adv. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3641","DOI":"10.1016\/j.febslet.2007.04.045","article-title":"ER chaperones in mammalian development and human diseases","volume":"581","author":"Ni","year":"2007","journal-title":"FEBS Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/nrneurol.2017.99","article-title":"ER stress and the unfolded protein response in neurodegneration","volume":"13","author":"Hetz","year":"2017","journal-title":"Nat. Rev. Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1042\/BJ20101864","article-title":"ER stress modulates celular metabolism","volume":"435","author":"Wang","year":"2011","journal-title":"Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.tcb.2003.11.001","article-title":"A trip to the ER: Coping with stress","volume":"14","author":"Rutkowski","year":"2004","journal-title":"Trends Cell. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"37375","DOI":"10.1074\/jbc.M303619200","article-title":"Induction of Grp78\/BiP by translational block: Activation of the Grp78 promoter by ATF4 through and upstream ATF\/CRE site independent of the endoplasmic reticulum stress elements","volume":"278","author":"Luo","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1042\/BJ20050374","article-title":"PERK (eIF2alpha kinase) is required to activate the stress-activated MAPKs and induce the expression of immediate-early genes upon disruption of ER calcium homoeostasis","volume":"393","author":"Liang","year":"2006","journal-title":"Biochem. J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/s41392-023-01570-w","article-title":"Endoplasmic reticulum stress: Molecular mechanism and therapeutic targets","volume":"8","author":"Chen","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1038\/cdd.2009.144","article-title":"Essential role of the unfolded protein response regulator GRP78\/BiP in protection from neuronal apoptosis","volume":"17","author":"Wang","year":"2010","journal-title":"Cell Death Differ."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4921","DOI":"10.1038\/onc.2012.514","article-title":"Endoplasmic reticulum ribosome-binding protein 1 (RRBP1) overexpression is frequently found in lung cancer patients and alleviates intracellular stress-induced apoptosis through the enhancement of GRP78","volume":"32","author":"Tsai","year":"2013","journal-title":"Oncogene"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Pl\u00fcmpe, T., Ehninger, D., Steiner, B., Klempin, F., Jessberger, S., Brandt, M., R\u00f6mer, B., Rodriguez, G.R., Kronenberg, G., and Kempermann, G. (2006). Variability of doublecortin-associated dendrite maturation in adult hippocampal neurogenesis is independent of the regulation of precursor cell proliferation. BMC Neurosci., 7.","DOI":"10.1186\/1471-2202-7-77"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Fan, Y., Si, Z., Wang, L., and Zhang, L. (2023). DYT-TOR1A dystonia: An update on pathogenesis and treatment. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1216929"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/S0197-0186(98)00023-0","article-title":"c-Fos as a transcription factor: A stressful (re)view from a functional map","volume":"33","year":"1998","journal-title":"Neurochem. Int."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1111\/j.1365-2826.2008.01734.x","article-title":"Measurement of immediate-early gene activation- c-fos and beyond","volume":"20","year":"2008","journal-title":"J. Neuroendocrinol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/0361-9230(93)90225-Z","article-title":"Stress-induced c-fos expression in the rat brain: Activation mechanism of sympathetic pathway","volume":"31","author":"Senba","year":"1993","journal-title":"Brain Res. Bull."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Khan, Z.U., Carretero-Rey, M., de Le\u00f3n-L\u00f3pez, C.A.M., and Navarro-Lobato, I. (2025). Memory-Associated Immediate Early Genes: Roles in Synaptic Function, Memory Processes, and Neurological Diseases. Mol. Neurobiol., in press.","DOI":"10.1007\/s12035-025-05203-x"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Kania, E., Paj\u0105k, B., and Orzechowski, A. (2015). Calcium homeostasis and ER stress in control of autophagy in cancer cells. Biomed. Res. Int., 2015.","DOI":"10.1155\/2015\/352794"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Minatohara, K., Akiyoshi, M., and Okuno, H. (2016). Role of Immediate-Early Genes in Synaptic Plasticity and Neuronal Ensembles Underlying the Memory Trace. Front. Mol. Neurosci., 8.","DOI":"10.3389\/fnmol.2015.00078"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/0896-6273(90)90106-P","article-title":"The regulation and function of c-fos and other immediate early genes in the nervous system","volume":"4","author":"Sheng","year":"1990","journal-title":"Neuron"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.neuro.2018.12.009","article-title":"Mechanistic comparison Between MPTP and rotenone neurotoxicity in mice","volume":"71","author":"Bhurtel","year":"2019","journal-title":"Neurotoxicology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.cell.2005.10.037","article-title":"Identification of intrinsic determinants of midbrain dopamine neurons","volume":"124","author":"Andersson","year":"2006","journal-title":"Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1007\/s12031-015-0710-7","article-title":"Mitochondrial c-Fos May Increase the Vulnerability of Neuro2a Cells to Cellular Stressors","volume":"59","author":"Kambe","year":"2016","journal-title":"J. Mol. Neurosci."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Rodriguez-Losada, N., Romero, P., Estivill-Torr\u00fas, G., Guzm\u00e1n de Villoria, R., and Aguirre, J.A. (2017). Cell survival and differentiation with nanocrystalline glass-like carbon using substantia nigra dopaminergic cells derived from transgenic mouse embryos. PLoS ONE, 12.","DOI":"10.24310\/riuma.13226"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1021\/ja01539a017","article-title":"Preparation of Graphitic Oxide","volume":"80","author":"Hummers","year":"1958","journal-title":"J. Am. Chem. Soc."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"14382","DOI":"10.1039\/D1NR02927D","article-title":"Effect of the reduced graphene oxide (rGO) compaction degree and concentration on rGO-polymer composite printability and cell interactions","volume":"13","author":"Sinha","year":"2021","journal-title":"Nanoscale"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1523\/JNEUROSCI.19-01-00010.1999","article-title":"Neuroprotection and neuronal differentiation studies using substantia nigra dopaminergic cells derived from transgenic mouse embryos","volume":"19","author":"Son","year":"1999","journal-title":"J. Neurosci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/0301-4622(90)80040-E","article-title":"Denaturation behaviour of DNA-protein-complexes detected in situ in metaphase chromosomes in suspension by Hoechst 33258 fluorescence","volume":"38","author":"Schaller","year":"1990","journal-title":"Biophys. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/j.bbadis.2014.03.010","article-title":"Involvement of IGF-II receptors in the antioxidant and neuroprotective effects of IGF-II on adult cortical neuronal cultures","volume":"1842","author":"Pavia","year":"2014","journal-title":"Biochim. Biophys. Acta"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/18\/8821\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:43:24Z","timestamp":1760035404000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/18\/8821"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,10]]},"references-count":64,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ijms26188821"],"URL":"https:\/\/doi.org\/10.3390\/ijms26188821","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,10]]}}}