{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T12:03:54Z","timestamp":1785240234081,"version":"3.55.0"},"reference-count":55,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T00:00:00Z","timestamp":1748044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Polish National Science Centre","doi-asserted-by":"publisher","award":["2019\/35\/O\/NZ5\/02270"],"award-info":[{"award-number":["2019\/35\/O\/NZ5\/02270"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Multiple sclerosis (MS) is a neuroinflammatory disease where oxidative stress and DNA damage may influence disease progression. We investigated whether defects in base excision repair (BER) pathways contribute to MS by combining functional DNA repair assays, gene expression profiling, and genotype analysis. We collected peripheral blood mononuclear cells from 70 MS patients and 61 healthy controls. These cells were subjected to tert-butyl hydroperoxide (TBH)-induced oxidative stress, and comet assay kinetics were measured over a period of 60 min. Additionally, we quantified the mRNA expression of nine key BER genes and genotyped selected polymorphisms related to DNA repair capacity. Samples from MS patients exhibited significantly higher levels of TBH-induced DNA lesions and displayed a distinct repair trajectory over time, as indicated by area-under-the-curve (AUC) analyses (p &lt; 0.001). The transcripts of MBD4 and NTHL1 were notably reduced in MS patients compared to those in the controls (p &lt; 0.0001). A logistic regression analysis revealed an association between the specific BER-related single nucleotide polymorphisms (SNPs) rs3087404, rs4135054, and rs1052133 and ineffective DNA repair. Subset analyses of B cells, CD4+ cells, and CD8+ cells further supported the presence of altered repair kinetics in MS, even though some subsets exhibited similar baseline lesion levels. Our findings suggest that impaired oxidative DNA repair is present in MS, likely driven by functional deficits in repair kinetics and alterations in the expression of BER genes and polymorphisms. This integrated approach highlights DNA repair pathways as potential therapeutic or prognostic targets in MS.<\/jats:p>","DOI":"10.3390\/biom15060756","type":"journal-article","created":{"date-parts":[[2025,5,25]],"date-time":"2025-05-25T20:39:36Z","timestamp":1748205576000},"page":"756","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Oxidative DNA Damage and Repair Dynamics in Multiple Sclerosis: Insights from Comet Assay Kinetics, Base Excision Repair Gene Expression, and Genotype Analysis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4166-5650","authenticated-orcid":false,"given":"Beata","family":"Filipek","sequence":"first","affiliation":[{"name":"Department of Microbiology and Pharmaceutical Biochemistry, Medical University of Lodz, Mazowiecka 5, 92-215 Lodz, Poland"},{"name":"Department of Neurology, Medical University of Lodz, Kopcinskiego 22, 90-153 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6056-7808","authenticated-orcid":false,"given":"Anna","family":"Macieja","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Pharmaceutical Biochemistry, Medical University of Lodz, Mazowiecka 5, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6173-4525","authenticated-orcid":false,"given":"Aleksandra","family":"Binda","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Mazowiecka 5, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6646-2203","authenticated-orcid":false,"given":"Rafal","family":"Szelenberger","sequence":"additional","affiliation":[{"name":"Biohazard Prevention Centre, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9873-9521","authenticated-orcid":false,"given":"Leslaw","family":"Gorniak","sequence":"additional","affiliation":[{"name":"Biohazard Prevention Centre, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7029-1857","authenticated-orcid":false,"given":"Elzbieta","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Neurological Rehabilitation, Medical University of Lodz, Milionowa 14, 93-113 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6779-308X","authenticated-orcid":false,"given":"Mariola","family":"Swiderek-Matysiak","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Lodz, Kopcinskiego 22, 90-153 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2582-1708","authenticated-orcid":false,"given":"Mariusz","family":"Stasiolek","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Lodz, Kopcinskiego 22, 90-153 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ireneusz","family":"Majsterek","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Mazowiecka 5, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2300-7339","authenticated-orcid":false,"given":"Tomasz","family":"Poplawski","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Pharmaceutical Biochemistry, Medical University of Lodz, Mazowiecka 5, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"380","DOI":"10.7861\/clinmed.2020-0292","article-title":"Clinical Presentation and Diagnosis of Multiple Sclerosis","volume":"20","author":"Ford","year":"2020","journal-title":"Clin. Med. Lond. Engl."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1097\/WCO.0000000000000622","article-title":"Multiple Sclerosis: Clinical Aspects","volume":"31","author":"Oh","year":"2018","journal-title":"Curr. Opin. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1474-4422(17)30470-2","article-title":"Diagnosis of Multiple Sclerosis: 2017 Revisions of the McDonald Criteria","volume":"17","author":"Thompson","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1126\/science.abj8222","article-title":"Longitudinal Analysis Reveals High Prevalence of Epstein-Barr Virus Associated with Multiple Sclerosis","volume":"375","author":"Bjornevik","year":"2022","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1136\/jnnp-2024-334062","article-title":"Vitamin D Affects the Risk of Disease Activity in Multiple Sclerosis","volume":"96","author":"Giordano","year":"2025","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10528-020-10010-1","article-title":"Vitamin D and Genetic Susceptibility to Multiple Sclerosis","volume":"59","author":"Scazzone","year":"2021","journal-title":"Biochem. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Schreiner, T.-G., and Genes, T.-M. (2021). Obesity and Multiple Sclerosis-A Multifaceted Association. J. Clin. Med., 10.","DOI":"10.3390\/jcm10122689"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1038\/nm1651","article-title":"Human TH17 Lymphocytes Promote Blood-Brain Barrier Disruption and Central Nervous System Inflammation","volume":"13","author":"Kebir","year":"2007","journal-title":"Nat. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.cell.2018.08.011","article-title":"Memory B Cells Activate Brain-Homing, Autoreactive CD4+ T Cells in Multiple Sclerosis","volume":"175","author":"Jelcic","year":"2018","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1093\/brain\/awr128","article-title":"Oxidative Damage in Multiple Sclerosis Lesions","volume":"134","author":"Haider","year":"2011","journal-title":"Brain J. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Jim\u00e9nez-Jim\u00e9nez, F.J., Alonso-Navarro, H., Salgado-C\u00e1mara, P., Garc\u00eda-Mart\u00edn, E., and Ag\u00fandez, J.A.G. (2024). Oxidative Stress Markers in Multiple Sclerosis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25126289"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.jns.2008.06.029","article-title":"Neurodegeneration in Multiple Sclerosis: The Role of Oxidative Stress and Excitotoxicity","volume":"274","author":"Gonsette","year":"2008","journal-title":"J. Neurol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/bs.ircmb.2021.05.002","article-title":"Significance of Base Excision Repair to Human Health","volume":"364","author":"Zhao","year":"2021","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1093\/aje\/kwq086","article-title":"Variation Within DNA Repair Pathway Genes and Risk of Multiple Sclerosis","volume":"172","author":"Briggs","year":"2010","journal-title":"Am. J. Epidemiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1385\/MB:26:3:249","article-title":"The Comet Assay for DNA Damage and Repair: Principles, Applications, and Limitations","volume":"26","author":"Collins","year":"2004","journal-title":"Mol. Biotechnol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7185","DOI":"10.1212\/WNL.0000000000208336","article-title":"Elevated Level of DNA Damage and Impaired Repair of DNA Oxidative Damage in Multiple Sclerosis Patients (P7-6.010)","volume":"102","author":"Filipek","year":"2024","journal-title":"Neurology"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Galita, G., Brzezi\u0144ska, O., Gulbas, I., Sarnik, J., Poplawska, M., Makowska, J., and Poplawski, T. (2020). Increased Sensitivity of PBMCs Isolated from Patients with Rheumatoid Arthritis to DNA Damaging Agents Is Connected with Inefficient DNA Repair. J. Clin. Med., 9.","DOI":"10.3390\/jcm9040988"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Galita, G., Sarnik, J., Zajac, G., Brzezinska, O., Budlewski, T., Poplawska, M., Przyby\u0142owska-Sygut, K., Joanna, M.S., and Poplawski, T. (2023). The Association between Inefficient Repair of Oxidative DNA Lesions and Common Polymorphisms of the Key Base Excision Repair Genes as Well as Their Expression Levels in Patients with Rheumatoid Arthritis. Arch. Med. Sci.","DOI":"10.5114\/aoms\/163133"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1093\/nar\/29.9.e45","article-title":"A New Mathematical Model for Relative Quantification in Real-Time RT\u2013PCR","volume":"29","author":"Pfaffl","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s13353-013-0173-x","article-title":"Reference Genes in Real-Time PCR","volume":"54","author":"Kozera","year":"2013","journal-title":"J. Appl. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.ymeth.2009.11.001","article-title":"How to Do Successful Gene Expression Analysis Using Real-Time PCR","volume":"50","author":"Derveaux","year":"2010","journal-title":"Methods San. Diego Calif."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1373\/clinchem.2008.112797","article-title":"The MIQE Guidelines: Minimum Information for Publication of Quantitative Real-Time PCR Experiments","volume":"55","author":"Bustin","year":"2009","journal-title":"Clin. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/j.dnarep.2013.07.011","article-title":"Measurement of DNA Base and Nucleotide Excision Repair Activities in Mammalian Cells and Tissues Using the Comet Assay\u2014A Methodological Overview","volume":"12","author":"Azqueta","year":"2013","journal-title":"DNA Repair"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ladeira, C., M\u00f8ller, P., Giovannelli, L., Gajski, G., Haveric, A., Bankoglu, E.E., Azqueta, A., Geri\u0107, M., Stopper, H., and Cab\u00eada, J. (2024). The Comet Assay as a Tool in Human Biomonitoring Studies of Environmental and Occupational Exposure to Chemicals\u2014A Systematic Scoping Review. Toxics, 12.","DOI":"10.3390\/toxics12040270"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1093\/mutage\/18.2.159","article-title":"Statistics of the Comet Assay: A Key to Discriminate between Genotoxic Effects","volume":"18","author":"Duez","year":"2003","journal-title":"Mutagenesis"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/S1473-3099(13)70324-4","article-title":"Strengthening the Reporting of Molecular Epidemiology for Infectious Diseases (STROME-ID): An Extension of the STROBE Statement","volume":"14","author":"Field","year":"2014","journal-title":"Lancet Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.mrrev.2019.03.002","article-title":"Working Group 5 of the hCOMET project (CA15132) DNA Repair as a Human Biomonitoring Tool: Comet Assay Approaches","volume":"781","author":"Azqueta","year":"2019","journal-title":"Mutat. Res. Rev. Mutat. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1080\/02664763.2021.1891527","article-title":"Robust Inference for Skewed Data in Health Sciences","volume":"49","author":"Nandy","year":"2022","journal-title":"J. Appl. Stat."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1515\/revneuro-2023-0091","article-title":"Oxidative Stress Involvement in the Molecular Pathogenesis and Progression of Multiple Sclerosis: A Literature Review","volume":"35","year":"2024","journal-title":"Rev. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s12974-024-03016-8","article-title":"Mitochondrial and Metabolic Dysfunction of Peripheral Immune Cells in Multiple Sclerosis","volume":"21","author":"Wang","year":"2024","journal-title":"J. Neuroinflamm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1093\/brain\/aws012","article-title":"NADPH Oxidase Expression in Active Multiple Sclerosis Lesions in Relation to Oxidative Tissue Damage and Mitochondrial Injury","volume":"135","author":"Fischer","year":"2012","journal-title":"Brain J. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"eadk0865","DOI":"10.1126\/sciimmunol.adk0865","article-title":"Oxidative Phosphorylation Regulates B Cell Effector Cytokines and Promotes Inflammation in Multiple Sclerosis","volume":"9","author":"Li","year":"2024","journal-title":"Sci. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1177\/135245859800400503","article-title":"Oxidative Damage to DNA in Plaques of MS Brains","volume":"4","author":"Vladimirova","year":"1998","journal-title":"Mult. Scler. Houndmills Basingstoke Engl."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"S571","DOI":"10.4103\/jpbs.jpbs_32_23","article-title":"Patient\u2019s Knowledge and Perception of Endodontics Treatment: An Observational Study","volume":"15","author":"Manasa","year":"2023","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.jns.2011.09.004","article-title":"Peroxidation of Lipoproteins in Multiple Sclerosis","volume":"311","author":"Ferretti","year":"2011","journal-title":"J. Neurol. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.expneurol.2015.11.010","article-title":"Oxidative Stress in Multiple Sclerosis: Central and Peripheral Mode of Action","volume":"277","author":"Ohl","year":"2016","journal-title":"Exp. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2584","DOI":"10.1091\/mbc.E18-10-0650","article-title":"NAD+ Consumption by PARP1 in Response to DNA Damage Triggers Metabolic Shift Critical for Damaged Cell Survival","volume":"30","author":"Murata","year":"2019","journal-title":"Mol. Biol. Cell"},{"key":"ref_38","first-page":"1133","article-title":"A Germline MBD4 Mutation Was Identified in a Patient with Colorectal Oligopolyposis and Early-onset Cancer: A Case Report","volume":"42","author":"Tanakaya","year":"2019","journal-title":"Oncol. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"102920","DOI":"10.1016\/j.dnarep.2020.102920","article-title":"NTHL1 in Genomic Integrity, Aging and Cancer","volume":"93","author":"Das","year":"2020","journal-title":"DNA Repair"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"di Penta, A., Moreno, B., Reix, S., Fernandez-Diez, B., Villanueva, M., Errea, O., Escala, N., Vandenbroeck, K., Comella, J.X., and Villoslada, P. (2013). Oxidative Stress and Proinflammatory Cytokines Contribute to Demyelination and Axonal Damage in a Cerebellar Culture Model of Neuroinflammation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054722"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-D\u00edaz, C.A., Su\u00e1rez-Souto, M.A., P\u00e9rez-Soto, E., G\u00f3mez-L\u00f3pez, M., Mungu\u00eda-Cervantes, J.E., P\u00e9rez-Vielma, N.M., and S\u00e1nchez-Monroy, V. (2024). The Human 8-oxoG DNA Glycosylase 1 (OGG1) Ser326Cys Polymorphism in Infertile Men. Biomedicines, 12.","DOI":"10.3390\/biomedicines12102286"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4100","DOI":"10.1093\/nar\/gkh739","article-title":"Oxidative Damage to Methyl-CpG Sequences Inhibits the Binding of the Methyl-CpG Binding Domain (MBD) of Methyl-CpG Binding Protein 2 (MeCP2)","volume":"32","author":"Valinluck","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1002\/mc.22073","article-title":"Genetic Variations in Base Excision Repair Pathway and Risk of Bladder Cancer: A Case-Control Study in the United States","volume":"54","author":"Xie","year":"2015","journal-title":"Mol. Carcinog."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Stratigopoulou, M., van Dam, T.P., and Guikema, J.E.J. (2020). Base Excision Repair in the Immune System: Small DNA Lesions With Big Consequences. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01084"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"W\u00f3jcik, P., G\u0119gotek, A., \u017darkovi\u0107, N., and Skrzydlewska, E. (2021). Oxidative Stress and Lipid Mediators Modulate Immune Cell Functions in Autoimmune Diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020723"},{"key":"ref_46","first-page":"25","article-title":"XPC Deficiency Is Related to APE1 and OGG1 Expression and Function","volume":"784","author":"Lajus","year":"2016","journal-title":"Mutat. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e170660","DOI":"10.1172\/JCI170660","article-title":"Polymerase \u03b8 Inhibition Steps on the cGAS Pedal","volume":"133","author":"Smith","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"101808","DOI":"10.1016\/j.smim.2023.101808","article-title":"Mitochondria during T Cell Aging","volume":"69","author":"Mittelbrunn","year":"2023","journal-title":"Semin. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1089\/neu.2015.3881","article-title":"Plasma Anti-Glial Fibrillary Acidic Protein Autoantibody Levels during the Acute and Chronic Phases of Traumatic Brain Injury: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot Study","volume":"33","author":"Wang","year":"2016","journal-title":"J. Neurotrauma"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Ellen, O., Ye, S., Nheu, D., Dass, M., Pagnin, M., Ozturk, E., Theotokis, P., Grigoriadis, N., and Petratos, S. (2023). The Heterogeneous Multiple Sclerosis Lesion: How Can We Assess and Modify a Degenerating Lesion?. Int. J. Mol. Sci., 24.","DOI":"10.20944\/preprints202305.1549.v1"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Shaw, P., Kumar, N., Sahun, M., Smits, E., Bogaerts, A., and Privat-Maldonado, A. (2022). Modulating the Antioxidant Response for Better Oxidative Stress-Inducing Therapies: How to Take Advantage of Two Sides of the Same Medal?. Biomedicines, 10.","DOI":"10.3390\/biomedicines10040823"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.2147\/CLEP.S376005","article-title":"The Epidemiology, Treatment Patterns and Economic Burden of Different Phenotypes of Multiple Sclerosis in Italy: Relapsing-Remitting Multiple Sclerosis and Secondary Progressive Multiple Sclerosis","volume":"14","author":"Perrone","year":"2022","journal-title":"Clin. Epidemiol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Tian, G., Katchur, S.R., Jiang, Y., Briand, J., Schaber, M., Kreatsoulas, C., Schwartz, B., Thrall, S., Davis, A.M., and Duvall, S. (2022). Small Molecule-Mediated Allosteric Activation of the Base Excision Repair Enzyme 8-Oxoguanine DNA Glycosylase and Its Impact on Mitochondrial Function. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-18878-2"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"103827","DOI":"10.1016\/j.dnarep.2025.103827","article-title":"Modulation of OGG1 Enzymatic Activities by Small Molecules, Promising Tools and Current Challenges","volume":"149","author":"Renaudin","year":"2025","journal-title":"DNA Repair"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1759091419899782","DOI":"10.1177\/1759091419899782","article-title":"NRF2 as a Therapeutic Target in Neurodegenerative Diseases","volume":"12","author":"Brandes","year":"2020","journal-title":"ASN Neuro"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/6\/756\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:39:36Z","timestamp":1760031576000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/6\/756"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,24]]},"references-count":55,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["biom15060756"],"URL":"https:\/\/doi.org\/10.3390\/biom15060756","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,24]]}}}