{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T22:24:33Z","timestamp":1791584673016,"version":"4.3.4"},"reference-count":118,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Neurodegenerative diseases are characterized by progressive neuronal dysfunction, often accompanied by chronic inflammatory states and redox imbalance within the central nervous system (CNS). Glutathione (GSH), a key regulator of oxidative stress and cellular immunity, has a critical role in modulating the functional states of CNS-resident and infiltrating immune cell subsets. This review aims to synthesize emerging evidence on how GSH depletion contributes to impaired immune and antioxidant activity in neurodegenerative diseases, such as Parkinson\u2019s Disease (PD), Alzheimer\u2019s Disease (AD), and multiple sclerosis (MS). By exploring how redox signaling via GSH influences inflammatory immune phenotypes across different disease states, we will isolate possible therapeutic interventions for treatment of these conditions. By characterizing GSH\u2019s function and designating it as a special regulator of immune cell behavior, this review highlights its potential as both a therapeutic agent and biomarker for patients with neurodegenerative conditions.<\/jats:p>","DOI":"10.3389\/fphar.2025.1737199","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T06:25:44Z","timestamp":1768458344000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Glutathione and neurodegenerative diseases: immunopharmacological implications"],"prefix":"10.3389","volume":"16","author":[{"given":"Ethan","family":"Knudsen","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences","place":["Pomona, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaxson","family":"Tadje","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences","place":["Pomona, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carter","family":"Coggins","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences","place":["Pomona, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishwanath","family":"Venketaraman","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences","place":["Pomona, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.nbd.2009.07.030","article-title":"Structure and function of the blood\u2013brain barrier","volume":"37","author":"Abbott","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2015\/151979","article-title":"Tau hyperphosphorylation and oxidative stress, a critical vicious circle in neurodegenerative tauopathies?","volume":"2015","author":"Alavi Naini","year":"2015","journal-title":"Oxidative Med. Cell. Longev."},{"key":"B3","doi-asserted-by":"publisher","first-page":"5010","DOI":"10.3390\/ijms22095010","article-title":"Glutathione in the brain","volume":"22","author":"Aoyama","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"196","DOI":"10.3389\/fphar.2014.00196","article-title":"Glutathione: new roles in redox signaling for an old antioxidant","volume":"5","author":"Aquilano","year":"2014","journal-title":"Front. Pharmacol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1093\/cei\/uxac123","article-title":"Treg specialization and functions beyond immune suppression","volume":"211","author":"Astarita","year":"2023","journal-title":"Clin. Exp. Immunol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/bs.vh.2022.09.002","article-title":"The antioxidant glutathione","volume":"121","author":"Averill-Bates","year":"2023","journal-title":"Vitamins Hormones"},{"key":"B7","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1007\/s10059-011-0276-3","article-title":"Regulation of reactive oxygen species generation in cell signaling","volume":"32","author":"Bae","year":"2011","journal-title":"Mol. Cells"},{"key":"B8","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1111\/ene.14108","article-title":"Parkinson disease","volume":"27","author":"Balestrino","year":"2020","journal-title":"Eur. J. Neurology"},{"key":"B9","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1016\/j.neubiorev.2020.10.004","article-title":"The glutathione system in Parkinson\u2019s disease and its progression","volume":"120","author":"Bj\u00f8rklund","year":"2021","journal-title":"Neurosci. and Biobehav. Rev."},{"key":"B10","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nrn2038","article-title":"Microglia-mediated neurotoxicity: uncovering the molecular mechanisms","volume":"8","author":"Block","year":"2007","journal-title":"Nat. Rev. Neurosci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.3390\/antiox10091407","article-title":"In vivo brain GSH: MRS methods and clinical applications","volume":"10","author":"Bottino","year":"2021","journal-title":"Antioxidants"},{"key":"B12","doi-asserted-by":"publisher","first-page":"5789","DOI":"10.3390\/molecules25245789","article-title":"Comprehensive review on Alzheimer\u2019s disease: causes and treatment","volume":"25","author":"Breijyeh","year":"2020","journal-title":"Molecules"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1264842","DOI":"10.3389\/fphar.2023.1264842","article-title":"Novel potential pharmacological applications of dimethyl fumarate\u2014an overview and update","volume":"14","author":"Bresciani","year":"2023","journal-title":"Front. Pharmacol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"7118","DOI":"10.1128\/JVI.00603-16","article-title":"Glutathione depletion is linked with Th2 polarization in mice with a retrovirus-induced immunodeficiency syndrome, murine AIDS: role of proglutathione molecules as immunotherapeutics","volume":"90","author":"Brundu","year":"2016","journal-title":"J. Virology"},{"key":"B15","doi-asserted-by":"publisher","first-page":"734229","DOI":"10.3389\/fimmu.2021.734229","article-title":"Reactive oxygen species in macrophages: sources and targets","volume":"12","author":"Canton","year":"2021","journal-title":"Front. Immunol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1177\/1352458514533400","article-title":"Glutathione in multiple sclerosis: more than just an antioxidant?","volume":"20","author":"Carvalho","year":"2014","journal-title":"Mult. Scler."},{"key":"B17","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1111\/j.1471-4159.2009.06319.x","article-title":"The blood\u2013brain barrier in neurodegenerative disease: a rhetorical perspective","volume":"111","author":"Carvey","year":"2009","journal-title":"J. Neurochem."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1553","DOI":"10.3390\/antiox12081553","article-title":"Glutathione and glutaredoxin\u2014key players in cellular redox homeostasis and signaling","volume":"12","author":"Chai","year":"2023","journal-title":"Antioxidants (Basel)"},{"key":"B19","doi-asserted-by":"publisher","first-page":"13997","DOI":"10.1523\/JNEUROSCI.3885-07.2007","article-title":"Inducible alterations of glutathione levels in adult dopaminergic midbrain neurons result in nigrostriatal degeneration","volume":"27","author":"Chinta","year":"2007","journal-title":"J. Neurosci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1177\/1352458517711568","article-title":"In vivo evidence of oxidative stress in brains of patients with progressive multiple sclerosis","volume":"24","author":"Choi","year":"2018","journal-title":"Multiple Scler. J."},{"key":"B21","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1016\/j.redox.2018.01.008","article-title":"13 reasons why the brain is susceptible to oxidative stress","volume":"15","author":"Cobley","year":"2018","journal-title":"Redox Biol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1007\/s10875-008-9236-x","article-title":"Multiple sclerosis and regulatory T cells","volume":"28","author":"Costantino","year":"2008","journal-title":"J. Clin. Immunol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"18","DOI":"10.3390\/biomedicines13010018","article-title":"Oxidative stress, glutathione insufficiency, and inflammatory pathways in type 2 diabetes mellitus: implications for therapeutic interventions","volume":"13","author":"Dawi","year":"2024","journal-title":"Biomedicines"},{"key":"B24","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1046\/j.1365-2362.2000.00736.x","article-title":"N-acetylcysteine replenishes glutathione in HIV infection","volume":"30","author":"De Rosa","year":"2000","journal-title":"Eur. J. Clin. Investigation"},{"key":"B25","doi-asserted-by":"publisher","first-page":"461","DOI":"10.3233\/JPD-130230","article-title":"The role of oxidative stress in Parkinson\u2019s disease","volume":"3","author":"Dias","year":"2013","journal-title":"J. Parkinson\u2019s Dis."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.3389\/fimmu.2017.01239","article-title":"Glutathione fine-tunes the innate immune response toward antiviral pathways in a macrophage cell line independently of its antioxidant properties","volume":"8","author":"Diotallevi","year":"2017","journal-title":"Front. Immunol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s12276-017-0013-x","article-title":"Glutathione disulfide sensitizes hepatocytes to TNF\u03b1-mediated cytotoxicity via IKK-\u03b2 S-glutathionylation: a potential mechanism underlying non-alcoholic fatty liver disease","volume":"50","author":"Dou","year":"2018","journal-title":"Exp. and Mol. Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"e70073","DOI":"10.1111\/jnc.70073","article-title":"Glutathione metabolism of the brain\u2014the role of astrocytes","volume":"169","author":"Dringen","year":"2025","journal-title":"J. Neurochem."},{"key":"B29","doi-asserted-by":"publisher","first-page":"2753","DOI":"10.3390\/nu16162753","article-title":"The role of S-glutathionylation in health and disease: a bird\u2019s eye view","volume":"16","author":"Federici","year":"2024","journal-title":"Nutrients"},{"key":"B30","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1080\/09674845.2013.11669939","article-title":"Glutathione in multiple sclerosis","volume":"70","author":"Ferreira","year":"2013","journal-title":"Br. J. Biomed. Sci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"610813","DOI":"10.1155\/2015\/610813","article-title":"Interrelation of oxidative stress and inflammation in neurodegenerative disease: role of TNF","volume":"2015","author":"Fischer","year":"2015","journal-title":"Oxidative Med. Cell. Longev."},{"key":"B32","doi-asserted-by":"publisher","first-page":"3603","DOI":"10.3390\/ijms22073603","article-title":"Intracellular redox-modulated pathways as targets for effective approaches in the treatment of viral infection","volume":"22","author":"Fraternale","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1016\/0028-3908(96)84626-0","article-title":"Selective role of glutathione in protecting human neuronal cells from dopamine-induced apoptosis","volume":"35","author":"Gabby","year":"1996","journal-title":"Neuropharmacology"},{"key":"B34","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1017\/S1461145710000805","article-title":"Decreased levels of glutathione, the major brain antioxidant, in post-mortem prefrontal cortex from patients with psychiatric disorders","volume":"14","author":"Gawryluk","year":"2011","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"105","DOI":"10.2147\/IJGM.S15618","article-title":"Role of glutathione in immunity and inflammation in the lung","volume":"4","author":"Ghezzi","year":"2011","journal-title":"Int. J. Gen. Med."},{"key":"B36","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1016\/j.freeradbiomed.2017.08.008","article-title":"Assessment of glutathione\/glutathione disulphide ratio and S-glutathionylated proteins in human blood, solid tissues, and cultured cells","volume":"112","author":"Giustarini","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.3390\/antiox14091033","article-title":"Current insights into glutathione depletion in adult septic patients","volume":"14","author":"Gomar","year":"2025","journal-title":"Antioxidants"},{"key":"B38","doi-asserted-by":"publisher","first-page":"e28378","DOI":"10.1371\/journal.pone.0028378","article-title":"Glutathione and adaptive immune responses against Mycobacterium tuberculosis infection in healthy and HIV infected individuals","volume":"6","author":"Guerra","year":"2011","journal-title":"PLOS ONE"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1634","DOI":"10.1111\/j.1471-4159.2006.03907.x","article-title":"Oxidative stress and neurodegeneration: where are we now?","volume":"97","author":"Halliwell","year":"2006","journal-title":"J. Neurochem."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1038\/s41598-023-27653-w","article-title":"Neuronal glutathione loss leads to neurodegeneration involving gasdermin activation","volume":"13","author":"Hashimoto","year":"2023","journal-title":"Sci. Rep."},{"key":"B41","doi-asserted-by":"publisher","first-page":"4153","DOI":"10.3390\/ijms23084153","article-title":"Crossing the blood-brain barrier: advances in nanoparticle technology for drug delivery in neuro-oncology","volume":"23","author":"Hersh","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.nbd.2006.10.007","article-title":"Mitochondrial dysfunction, peroxidation damage and changes in glutathione metabolism in PARK6","volume":"25","author":"Hoepken","year":"2007","journal-title":"Neurobiol. Dis."},{"key":"B43","doi-asserted-by":"publisher","first-page":"721","DOI":"10.3346\/jkms.2005.20.5.721Hristov","article-title":"Pharmacokinetics of glutathione and its metabolites in normal subjects","volume":"20","author":"Hong","year":"2005","journal-title":"J. Korean Med. Sci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"e29696","DOI":"10.7759\/cureus.29696","article-title":"The role of glutathione metabolism in chronic illness development and its potential use as a novel therapeutic target","volume":"14","author":"Hristov","year":"2022","journal-title":"Cureus"},{"key":"B45","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1161\/01.RES.80.3.383","article-title":"Oxidative stress-induced actin reorganization mediated by the p38 mitogen-activated protein kinase\/heat shock protein 27 pathway in vascular endothelial cells","volume":"80","author":"Huot","year":"1997","journal-title":"Circulation Res."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1780","DOI":"10.1016\/j.cell.2018.10.001","article-title":"Distinct regulation of Th17 and Th1 cell differentiation by glutaminase-dependent metabolism","volume":"175","author":"Johnson","year":"2018","journal-title":"Cell"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.3390\/antiox11051026","article-title":"Randomized clinical trial of how long-term glutathione supplementation offers protection from oxidative damage and improves HbA1c in elderly type 2 diabetic patients","volume":"11","author":"Kalamkar","year":"2022","journal-title":"Antioxidants"},{"key":"B48","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/S0955-0674(97)80068-3","article-title":"AP-1 function and regulation","volume":"9","author":"Karin","year":"1997","journal-title":"Curr. Opin. Cell Biol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1001\/archsurg.1985.01390320065013","article-title":"Decreased hepatic glutathione levels in septic shock: predisposition of hepatocytes to oxidative stress: an experimental approach","volume":"120","author":"Keller","year":"1985","journal-title":"Archives Surg."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1016\/j.jaci.2007.01.016","article-title":"Glutathione depletion inhibits dendritic cell maturation and delayed-type hypersensitivity: implications for systemic disease and immunosenescence","volume":"119","author":"Kim","year":"2007","journal-title":"J. Allergy Clin. Immunol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1016\/j.immuni.2017.03.022","article-title":"Caught in the cROSsfire: GSH controls T cell metabolic reprogramming","volume":"46","author":"Klein Geltink","year":"2017","journal-title":"Immunity"},{"key":"B52","article-title":"Alzheimer disease","volume-title":"StatPearls treasure","author":"Kumar","year":"2024"},{"key":"B53","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1016\/j.cmet.2020.03.004","article-title":"Glutathione restricts serine metabolism to preserve regulatory T cell function","volume":"31","author":"Kurniawan","year":"2020","journal-title":"Cell Metab."},{"key":"B54","doi-asserted-by":"publisher","first-page":"413","DOI":"10.3390\/antiox8090413","article-title":"Glutathione induced immune-stimulatory activity by promoting M1-Like macrophages polarization via potential ROS scavenging capacity","volume":"8","author":"Kwon","year":"2019","journal-title":"Antioxidants"},{"key":"B55","doi-asserted-by":"publisher","first-page":"a028936","DOI":"10.1101\/cshperspect.a028936","article-title":"Multiple sclerosis pathology","volume":"8","author":"Lassmann","year":"2018","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"B56","doi-asserted-by":"publisher","first-page":"6923","DOI":"10.3390\/ijms23136923","article-title":"Evidence for oxidative pathways in the pathogenesis of PD: are antioxidants candidate drugs to ameliorate disease progression?","volume":"23","author":"Leathem","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B57","doi-asserted-by":"publisher","first-page":"2533","DOI":"10.1096\/fj.09-149997","article-title":"Depletion of GSH in glial cells induces neurotoxicity: relevance to aging and degenerative neurological diseases","volume":"24","author":"Lee","year":"2010","journal-title":"FASEB J."},{"key":"B58","doi-asserted-by":"publisher","first-page":"155","DOI":"10.3389\/fimmu.2019.00155","article-title":"GSH-C4 acts as anti-inflammatory drug in different models of canonical and cell autonomous inflammation through NF\u03baB inhibition","volume":"10","author":"Limongi","year":"2019","journal-title":"Front. Immunol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"1839","DOI":"10.3390\/antiox10111839","article-title":"Plasma glutathione levels decreased with cognitive decline among people with mild cognitive impairment (MCI): a two-year prospective study","volume":"10","author":"Lin","year":"2021","journal-title":"Antioxidants"},{"key":"B60","doi-asserted-by":"publisher","first-page":"2952","DOI":"10.3390\/ijms25052952","article-title":"The role of glutathione in the management of cell-mediated immune responses in individuals with HIV","volume":"25","author":"Lin","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B61","doi-asserted-by":"publisher","first-page":"103702","DOI":"10.1016\/j.redox.2025.103702","article-title":"Redox-signaling in innate immune memory: similar mechanisms in animals\/humans and plants","volume":"84","author":"Lindermayr","year":"2025","journal-title":"Redox Biol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-\u03baB signaling in inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct. Target. Ther."},{"key":"B63","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1186\/s12951-025-03415-w","article-title":"Advances in brain-targeted delivery strategies and natural product-mediated enhancement of blood\u2013brain barrier permeability","volume":"23","author":"Liu","year":"2025","journal-title":"J. Nanobiotechnology"},{"key":"B64","doi-asserted-by":"publisher","first-page":"3143","DOI":"10.1016\/j.bbagen.2012.09.008","article-title":"Glutathione synthesis","volume":"1830","author":"Lu","year":"2013","journal-title":"Biochim. Biophys. Acta."},{"key":"B65","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/j.immuni.2017.03.019","article-title":"Glutathione primes T cell metabolism for inflammation","volume":"46","author":"Mak","year":"2017","journal-title":"Immunity"},{"key":"B66","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1016\/j.biopsych.2015.04.005","article-title":"Brain glutathione levels\u2014 a novel biomarker for mild cognitive impairment and Alzheimer\u2019s disease","volume":"78","author":"Mandal","year":"2015","journal-title":"Biol. Psychiatry"},{"key":"B67","doi-asserted-by":"publisher","first-page":"fcac215","DOI":"10.1093\/braincomms\/fcac215","article-title":"Hippocampal glutathione depletion with enhanced iron level in patients with mild cognitive impairment and Alzheimer\u2019s disease compared with healthy elderly participants","volume":"4","author":"Mandal","year":"2022","journal-title":"Brain Commun."},{"key":"B68","doi-asserted-by":"publisher","first-page":"2685","DOI":"10.1089\/ARS.2009.2695","article-title":"Mitochondrial glutathione, a key survival antioxidant","volume":"11","author":"Mar\u00ed","year":"2009","journal-title":"Antioxidants and Redox Signal."},{"key":"B69","doi-asserted-by":"publisher","first-page":"1080140","DOI":"10.3389\/fmolb.2022.1080140","article-title":"Glutathione S-transferases control astrocyte activation and neuronal health during neuroinflammation","volume":"9","author":"Matoba","year":"2023","journal-title":"Front. Mol. Biosci."},{"key":"B70","doi-asserted-by":"publisher","first-page":"46","DOI":"10.15386\/mpr-2821","article-title":"Evaluation of oxidative stress biomarkers for differentiating bacterial and viral infections: a comparative study of glutathione disulfide (GSSG) and reduced glutathione (GSH)","volume":"98","author":"Milhelm","year":"2025","journal-title":"Med. Pharm. Rep."},{"key":"B71","doi-asserted-by":"publisher","first-page":"9409363","DOI":"10.1155\/2016\/9409363","article-title":"Glutathione as a biomarker in parkinson\u2019s disease: associations with aging and disease severity","volume":"2016","author":"Mischley","year":"2016","journal-title":"Oxid. Med. Cell Longev."},{"key":"B72","doi-asserted-by":"publisher","first-page":"e15613","DOI":"10.1016\/j.heliyon.2023.e15613","article-title":"Influence of dose and exposition time in the effectiveness of N-Acetyl-l-cysteine treatment in A549 human epithelial cells","volume":"9","author":"Montero","year":"2023","journal-title":"Heliyon"},{"key":"B73","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1038\/cr.2010.178","article-title":"Crosstalk of reactive oxygen species and NF-\u03baB signaling","volume":"21","author":"Morgan","year":"2011","journal-title":"Cell Res."},{"key":"B74","doi-asserted-by":"publisher","first-page":"734125","DOI":"10.1155\/2012\/734125","article-title":"Unveiling the mechanisms for decreased glutathione in individuals with HIV infection","volume":"2012","author":"Morris","year":"2012","journal-title":"Clin. Dev. Immunol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1007\/s12035-014-8705-x","article-title":"The glutathione system: a new drug target in neuroimmune disorders","volume":"50","author":"Morris","year":"2014","journal-title":"Mol. Neurobiol."},{"key":"B76","doi-asserted-by":"publisher","first-page":"827263","DOI":"10.3389\/fnagi.2022.827263","article-title":"Neuroinflammation: a possible link between chronic vascular disorders and neurodegenerative diseases","volume":"14","author":"Moyse","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"B77","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.bbi.2023.09.017","article-title":"Measurement of brain glutathione with magnetic resonance spectroscopy in schizophrenia-spectrum disorders \u2014 a systematic review and meta-analysis","volume":"115","author":"Murray","year":"2024","journal-title":"Brain, Behav. Immun."},{"key":"B78","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1186\/s12974-017-1004-5","article-title":"Dendrimer-mediated delivery of N-acetyl cysteine to microglia in a mouse model of Rett syndrome","volume":"14","author":"Nance","year":"2017","journal-title":"J. Neuroinflammation"},{"key":"B79","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/j.it.2019.02.001","article-title":"Priming microglia for innate immune memory in the brain","volume":"40","author":"Neher","year":"2019","journal-title":"Trends Immunol."},{"key":"B80","doi-asserted-by":"publisher","first-page":"4196","DOI":"10.3390\/molecules25184196","article-title":"Measurement of glutathione as a tool for oxidative stress studies by high performance liquid chromatography","volume":"25","author":"Nuhu","year":"2020","journal-title":"Molecules"},{"key":"B81","doi-asserted-by":"publisher","first-page":"101975","DOI":"10.1016\/j.redox.2021.101975","article-title":"Glutaredoxin: discovery, redox defense and much more","volume":"43","author":"Ogata","year":"2021","journal-title":"Redox Biol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"e09575","DOI":"10.1016\/j.heliyon.2022.e09575","article-title":"Liposomes: an emerging carrier for targeting Alzheimer\u2019s and Parkinson\u2019s diseases","volume":"8","author":"Pandian","year":"2022","journal-title":"Heliyon"},{"key":"B83","doi-asserted-by":"publisher","first-page":"8059","DOI":"10.3390\/ijms24098059","article-title":"Appraising the role of astrocytes as suppliers of neuronal glutathione precursors","volume":"24","author":"P\u00e9rez-Sala","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B84","doi-asserted-by":"publisher","first-page":"3071","DOI":"10.1073\/pnas.95.6.3071","article-title":"Glutathione levels in antigen-presenting cells modulate Th1 versus Th2 response patterns","volume":"95","author":"Peterson","year":"1998","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B85","doi-asserted-by":"publisher","first-page":"7928","DOI":"10.1038\/s41598-018-26296-6","article-title":"Imaging glutathione depletion in the rat brain using ascorbate-derived hyperpolarized MR and PET probes","volume":"8","author":"Qin","year":"2018","journal-title":"Sci. Rep."},{"key":"B86","doi-asserted-by":"publisher","first-page":"151","DOI":"10.3389\/fphar.2014.00151","article-title":"Glutathione and mitochondria","volume":"5","author":"Ribas","year":"2014","journal-title":"Front. Pharmacol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.brainres.2015.03.018","article-title":"Targeting transporters: promoting blood-brain barrier repair in response to oxidative stress injury","volume":"1623","author":"Ronaldson","year":"2015","journal-title":"Brain Research"},{"key":"B88","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.1373\/clinchem.2006.067793","article-title":"Oxidized forms of glutathione in peripheral blood as biomarkers of oxidative stress","volume":"52","author":"Rossi","year":"2006","journal-title":"Clin. Chem."},{"key":"B89","doi-asserted-by":"publisher","first-page":"3705","DOI":"10.2147\/DDDT.S85302","article-title":"Targeting brain cells with glutathione-modulated nanoliposomes: in vitro and in vivo study","volume":"9","author":"Salem","year":"2015","journal-title":"Drug Des. Devel Ther."},{"key":"B90","doi-asserted-by":"publisher","first-page":"4128152","DOI":"10.1155\/2019\/4128152","article-title":"Oxidative stress indexes for diagnosis of health or disease in humans","volume":"2019","author":"S\u00e1nchez-Rodr\u00edguez","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"B91","doi-asserted-by":"publisher","first-page":"R453","DOI":"10.1016\/j.cub.2014.03.034","article-title":"ROS function in redox signaling and oxidative stress","volume":"24","author":"Schieber","year":"2014","journal-title":"Curr. Biol."},{"key":"B92","doi-asserted-by":"publisher","first-page":"932152","DOI":"10.3389\/fimmu.2022.932152","article-title":"Th17 cells and inflammation in neurological disorders: possible mechanisms of action","volume":"13","author":"Shi","year":"2022","journal-title":"Front. Immunol."},{"key":"B93","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1038\/s41580-020-0230-3","article-title":"Reactive oxygen species (ROS) as pleiotropic physiological signalling agents","volume":"21","author":"Sies","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B94","doi-asserted-by":"publisher","first-page":"590808","DOI":"10.1155\/2014\/590808","article-title":"Thioredoxin system regulation in the central nervous system: experimental models and clinical evidence","volume":"2014","author":"Silva-Adaya","year":"2014","journal-title":"Oxidative Med. Cell. Longev."},{"key":"B95","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1038\/ejcn.2017.132","article-title":"Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function","volume":"72","author":"Sinha","year":"2018","journal-title":"Eur. J. Clin. Nutr."},{"key":"B96","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.freeradbiomed.2013.05.001","article-title":"Glutathione metabolism and parkinson\u2019s disease","volume":"62","author":"Smeyne","year":"2013","journal-title":"Free Radic Biol. Med."},{"key":"B97","doi-asserted-by":"publisher","first-page":"792639","DOI":"10.1155\/2011\/792639","article-title":"Mitogen-activated protein kinases and reactive oxygen species: how can ROS activate MAPK pathways?","volume":"2011","author":"Son","year":"2011","journal-title":"J. Signal Transduct."},{"key":"B98","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/1740-2557-2-4","article-title":"N-acetyl-L-cysteine ameliorates the inflammatory disease process in experimental autoimmune encephalomyelitis in lewis rats","volume":"2","author":"Stanislaus","year":"2005","journal-title":"J. Autoimmune Dis."},{"key":"B99","article-title":"Multiple sclerosis","volume-title":"StatPearls treasure","author":"Tafti","year":"2024"},{"key":"B100","doi-asserted-by":"publisher","first-page":"170","DOI":"10.3390\/antiox11010170","article-title":"Neuroprotection and disease modification by astrocytes and microglia in parkinson disease","volume":"11","author":"Takahashi","year":"2022","journal-title":"Antioxidants"},{"key":"B101","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.3390\/antiox10091479","article-title":"Oxidative stress and beta amyloid in Alzheimer\u2019s disease: which comes first?","volume":"10","author":"Tamagno","year":"2021","journal-title":"Antioxidants"},{"key":"B102","doi-asserted-by":"publisher","first-page":"112999","DOI":"10.1016\/j.colsurfb.2022.112999","article-title":"Surface-modified lipid nanocarriers for crossing the blood-brain barrier (BBB): a current overview of active targeting in brain diseases","volume":"221","author":"Teixeira","year":"2023","journal-title":"Colloids Surf B Biointerfaces."},{"key":"B103","doi-asserted-by":"publisher","first-page":"4490","DOI":"10.3390\/ijms24054490","article-title":"Polarized anti-inflammatory mesenchymal stem cells increase hippocampal neurogenesis and improve cognitive function in aged mice","volume":"24","author":"Tfilin","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B104","doi-asserted-by":"publisher","first-page":"1867","DOI":"10.3390\/antiox12101867","article-title":"N-Acetylcysteine and its immunomodulatory properties in humans and domesticated animals","volume":"12","author":"Tieu","year":"2023","journal-title":"Antioxidants"},{"key":"B105","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1002\/ana.25303","article-title":"Dendrimer\u2013N-Acetyl-L-Cysteine modulates monophagocytic response in adrenoleukodystrophy","volume":"84","author":"Turk","year":"2018","journal-title":"Ann. Neurology"},{"key":"B106","doi-asserted-by":"publisher","first-page":"9303","DOI":"10.3390\/ijms24119303","article-title":"Expected and unexpected effects of pharmacological antioxidants","volume":"24","author":"Tyuryaeva","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B107","doi-asserted-by":"publisher","first-page":"364","DOI":"10.3390\/antiox10030364","article-title":"Changes in glutathione content in liver diseases: an update","volume":"10","author":"Vairetti","year":"2021","journal-title":"Antioxidants"},{"key":"B108","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/j.neuint.2012.05.019","article-title":"The role of amino acid transporters in GSH synthesis in the blood\u2013brain barrier and central nervous system","volume":"61","author":"Valdovinos-Flores","year":"2012","journal-title":"Neurochem. Int."},{"key":"B109","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1016\/j.neuroscience.2007.08.028","article-title":"Integrating glutathione metabolism and mitochondrial dysfunction with implications for Parkinson\u2019s disease: a dynamic model","volume":"149","author":"Vali","year":"2007","journal-title":"Neuroscience"},{"key":"B110","doi-asserted-by":"publisher","first-page":"834","DOI":"10.3390\/antiox12040834","article-title":"Cellular compartmentalization, glutathione transport and its relevance in some pathologies","volume":"12","author":"V\u00e1zquez-Meza","year":"2023","journal-title":"Antioxidants"},{"key":"B111","doi-asserted-by":"publisher","first-page":"1719","DOI":"10.1111\/bph.13426","article-title":"Microglia antioxidant systems and redox signalling","volume":"174","author":"Vilhardt","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"B112","doi-asserted-by":"publisher","first-page":"2993","DOI":"10.2147\/JIR.S306849","article-title":"N-Acetylcysteine as adjuvant therapy for COVID-19 \u2013 a perspective on the current state of the evidence","volume":"14","author":"Wong","year":"2021","journal-title":"J. Inflamm. Res."},{"key":"B113","volume-title":"Parkinson diseaseStatPearls treasure","author":"Zafar","year":"2023"},{"key":"B114","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1016\/j.expneurol.2006.09.004","article-title":"Characterization of intracellular elevation of glutathione (GSH) with glutathione monoethyl ester and GSH in brain and neuronal cultures: relevance to Parkinson\u2019s disease","volume":"203","author":"Zeevalk","year":"2007","journal-title":"Exp. Neurology"},{"key":"B115","doi-asserted-by":"publisher","first-page":"1820","DOI":"10.1021\/acsnano.3c10674","article-title":"Functionalized nanomaterials capable of crossing the blood\u2013brain barrier","volume":"18","author":"Zha","year":"2024","journal-title":"ACS Nano"},{"key":"B116","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1016\/j.semcdb.2012.03.017","article-title":"Glutathione synthesis and its role in redox signaling","volume":"23","author":"Zhang","year":"2012","journal-title":"Semin. Cell Dev. Biol."},{"key":"B117","doi-asserted-by":"publisher","first-page":"779","DOI":"10.4103\/NRR.NRR-D-23-01508","article-title":"Infiltration by monocytes of the CNS and its role in multiple sclerosis: reflections on therapeutic strategies","volume":"20","author":"Zhang","year":"2025","journal-title":"Neural Regen. Res."},{"key":"B118","doi-asserted-by":"publisher","first-page":"1247","DOI":"10.3892\/ol.2012.931","article-title":"Redox status expressed as GSH:GSSG ratio as a marker for oxidative stress in paediatric tumour patients","volume":"4","author":"Zitka","year":"2012","journal-title":"Oncol. Lett."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1737199\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T06:55:23Z","timestamp":1771916123000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1737199\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,15]]},"references-count":118,"alternative-id":["10.3389\/fphar.2025.1737199"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1737199","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,15]]},"article-number":"1737199"}}