INTERNATIONAL JOURNAL OF EVIDENCE-BASED MEDICINE
Review Article
Jun 29, 2026 133 73

Impact of Aging on Brain Redox Balance: Mechanistic Links to Synaptic Dysfunction and Neurodegenerative Disease

Esther Uyoyooghene Olokede 1 * ,
Leo Tata 2,
Agbolade Adedoyin Adeniji 3
1 Department of Medical Laboratory Science, Faculty of Basic Medical Sciences, University of Benin, Edo State, Nigeria2 Department of Human Development and Family Studies, College of Health and Human Sciences, Iowa State University, Ames, Iowa, USA3 Department of Medicine and Surgery, Lagos State University College of Medicine, Ikeja, Nigeria * Corresponding Author
International Journal of Evidence-Based Medicine, 1(2), 2026, jebm008, https://doi.org/10.63946/jebm/18873
Publication date: Jun 29, 2026
Full Text (PDF)

ABSTRACT

Aging remains the most significant risk factor driving the development and progression of neurodegenerative diseases, as it reflects the gradual accumulation of molecular and cellular changes over time. Disturbance of redox balance has been recognized among these changes as a primary mechanism that links aging to synaptic decline. The imbalance favoring the production of reactive oxygen species over the capability of the antioxidant systems to neutralize them results in oxidative stress, which selectively disrupts synaptic morphology and function. In this scenario mitochondrial dysfunction is a significant factor since it not only raises oxidative stress but also reduces the energy supply necessary for standard cellular activity. At the same time, the decline of the endogenous antioxidant system due to aging further weakens neuronal defense. Oxidative modification of synaptic proteins changes their composition and roles, thereby reducing neurotransmission and plasticity. These interconnected processes underlie the pathological basis of major neurodegenerative diseases, such as Parkinson's and Alzheimer's. The complexity of the involved systems restricts the success of redox-balance-restoring therapeutic strategies, although they have a high potential. Hence, further work is necessary to enhance redox-based therapies and facilitate their translation for neurodegeneration in aging.

KEYWORDS

Redox Homeostasis Oxidative Stress Brain Aging Synaptic Dysfunction Neurodegenerative Diseases Reactive Oxygen Species

CITATION (Vancouver)

Olokede EU, Tata L, Adeniji AA. Impact of Aging on Brain Redox Balance: Mechanistic Links to Synaptic Dysfunction and Neurodegenerative Disease. International Journal of Evidence-Based Medicine. 2026;1(2):jebm008. https://doi.org/10.63946/jebm/18873
APA
Olokede, E. U., Tata, L., & Adeniji, A. A. (2026). Impact of Aging on Brain Redox Balance: Mechanistic Links to Synaptic Dysfunction and Neurodegenerative Disease. International Journal of Evidence-Based Medicine, 1(2), jebm008. https://doi.org/10.63946/jebm/18873
Harvard
Olokede, E. U., Tata, L., and Adeniji, A. A. (2026). Impact of Aging on Brain Redox Balance: Mechanistic Links to Synaptic Dysfunction and Neurodegenerative Disease. International Journal of Evidence-Based Medicine, 1(2), jebm008. https://doi.org/10.63946/jebm/18873
AMA
Olokede EU, Tata L, Adeniji AA. Impact of Aging on Brain Redox Balance: Mechanistic Links to Synaptic Dysfunction and Neurodegenerative Disease. International Journal of Evidence-Based Medicine. 2026;1(2), jebm008. https://doi.org/10.63946/jebm/18873
Chicago
Olokede, Esther Uyoyooghene, Leo Tata, and Agbolade Adedoyin Adeniji. "Impact of Aging on Brain Redox Balance: Mechanistic Links to Synaptic Dysfunction and Neurodegenerative Disease". International Journal of Evidence-Based Medicine 2026 1 no. 2 (2026): jebm008. https://doi.org/10.63946/jebm/18873
MLA
Olokede, Esther Uyoyooghene et al. "Impact of Aging on Brain Redox Balance: Mechanistic Links to Synaptic Dysfunction and Neurodegenerative Disease". International Journal of Evidence-Based Medicine, vol. 1, no. 2, 2026, jebm008. https://doi.org/10.63946/jebm/18873

REFERENCES

  1. Hayashide L de S, Pessoa B, Dias G, Pontes B, Pinto RS, Diniz LP. From Neuron‐Centric to Glia‐Centric: How Aging Glial Networks Drive Neurodegenerative Disease. J Neurochem. 2026 Jan;170(1):e70361. PubMed PMID: 41591255; PubMed Central PMCID: PMC12839804.https://doi.org/10.1111/jnc.70361
  2. Chen YS, Tian HX, Rong DC, Wang L, Chen S, Zeng J, et al. ROS homeostasis in cell fate, pathophysiology, and therapeutic interventions. Mol Biomed. 2025 Oct 30;6:89. PubMed PMID: 41162811; PubMed Central PMCID: PMC12572517.https://doi.org/10.1186/s43556-025-00338-8
  3. Selvaraj NR, Nandan D, Nair BG, Nair VA, Venugopal P, Aradhya R. Oxidative Stress and Redox Imbalance: Common Mechanisms in Cancer Stem Cells and Neurodegenerative Diseases. Cells. 2025 Mar 29;14(7):511. PubMed PMID: 40214466; PubMed Central PMCID: PMC11988017.https://doi.org/10.3390/cells14070511
  4. Dash UC, Bhol NK, Swain SK, Samal RR, Nayak PK, Raina V, et al. Oxidative stress and inflammation in the pathogenesis of neurological disorders: Mechanisms and implications. Acta Pharm Sin B. 2025 Jan 1;15(1):15-34. https://doi.org/10.1016/j.apsb.2024.10.004
  5. Olufunmilayo EO, Gerke-Duncan MB, Holsinger RMD. Oxidative Stress and Antioxidants in Neurodegenerative Disorders. Antioxidants. 2023 Feb;12(2):517. https://doi.org/10.3390/antiox12020517
  6. Castelli S, Carinci E, Baldelli S. Oxidative Stress in Neurodegenerative Disorders: A Key Driver in Impairing Skeletal Muscle Health. Int J Mol Sci. 2025 Jun 16;26(12):5782. PubMed PMID: 40565245; PubMed Central PMCID: PMC12193302. https://doi.org/10.3390/ijms26125782
  7. Masenga SK, Kabwe LS, Chakulya M, Kirabo A. Mechanisms of Oxidative Stress in Metabolic Syndrome. Int J Mol Sci. 2023 Jan;24(9):7898. https://doi.org/10.3390/ijms24097898
  8. Rauf A, Khalil AA, Awadallah S, Khan SA, Abu‐Izneid T, Kamran M, et al. Reactive oxygen species in biological systems: Pathways, associated diseases, and potential inhibitors-A review. Food Sci Nutr. 2023 Dec 1;12(2):675-93. PubMed PMID: 38370049; PubMed Central PMCID: PMC10867483. https://doi.org/10.1002/fsn3.3784
  9. Martinez-Banaclocha MA. Targeting the Cysteine Redox Proteome in Parkinson's Disease: The Role of Glutathione Precursors and Beyond. Antioxidants. 2023 Jul;12(7):1373. https://doi.org/10.3390/antiox12071373
  10. Percio A, Cicchinelli M, Masci D, Summo M, Urbani A, Greco V. Oxidative Cysteine Post Translational Modifications Drive the Redox Code Underlying Neurodegeneration and Amyotrophic Lateral Sclerosis. Antioxidants. 2024 Aug;13(8):883. https://doi.org/10.3390/antiox13080883
  11. de la Lastra JMP, Andrés CMC, Munguira EB, Juan CA, Pérez-Lebeña E. Pathophysiology of reactive oxygen species (ROS). Arch Toxicol. 2026 Feb 1;100(2):475-513. https://doi.org/10.1007/s00204-025-04276-w
  12. Liu S, Liu J, Wang Y, Deng F, Deng Z. Oxidative Stress: Signaling Pathways, Biological Functions, and Disease. MedComm. 2025 Jul 1;6(7):e70268. PubMed PMID: 40599237; PubMed Central PMCID: PMC12209598. https://doi.org/10.1002/mco2.70268
  13. García-Domínguez M. Glial Cell Dynamics in Neuroinflammation: Mechanisms, Interactions, and Therapeutic Implications. Biomedicines. 2026 Jan 6;14(1):115. PubMed PMID: 41595651; PubMed Central PMCID: PMC12839156. https://doi.org/10.3390/biomedicines14010115
  14. Calì C, Cantando I, Veloz Castillo MF, Gonzalez L, Bezzi P. Metabolic Reprogramming of Astrocytes in Pathological Conditions: Implications for Neurodegenerative Diseases. Int J Mol Sci. 2024 Jan;25(16):8922. https://doi.org/10.3390/ijms25168922
  15. de Almeida AJPO, de Oliveira JCPL, da Silva Pontes LV, de Souza Júnior JF, Gonçalves TAF, Dantas SH, et al. ROS: Basic Concepts, Sources, Cellular Signaling, and its Implications in Aging Pathways. Oxid Med Cell Longev. 2022 Oct 19;2022:1225578. PubMed PMID: 36312897; PubMed Central PMCID: PMC9605829. https://doi.org/10.1155/2022/1225578
  16. Teleanu RI, Niculescu AG, Roza E, Vladâcenco O, Grumezescu AM, Teleanu DM. Neurotransmitters-Key Factors in Neurological and Neurodegenerative Disorders of the Central Nervous System. Int J Mol Sci. 2022 May 25;23(11):5954. PubMed PMID: 35682631; PubMed Central PMCID: PMC9180936. https://doi.org/10.3390/ijms23115954
  17. Biswas K, Alexander K, Francis MM. Reactive Oxygen Species: Angels and Demons in the Life of a Neuron. NeuroSci. 2022 Mar;3(1):130-45. https://doi.org/10.3390/neurosci3010011
  18. Stojanovic B, Milivojcevic Bevc I, Dimitrijevic Stojanovic M, Stojanovic BS, Lazarevic T, Spasic M, et al. Oxidative Stress, Inflammation, and Cellular Senescence in Neuropathic Pain: Mechanistic Crosstalk. Antioxidants. 2025 Oct;14(10):1166. https://doi.org/10.3390/antiox14101166
  19. Șerban M, Toader C, Covache-Busuioc RA. The Redox Revolution in Brain Medicine: Targeting Oxidative Stress with AI, Multi-Omics and Mitochondrial Therapies for the Precision Eradication of Neurodegeneration. Int J Mol Sci. 2025 Aug 3;26(15):7498. PubMed PMID: 40806624; PubMed Central PMCID: PMC12347410. https://doi.org/10.3390/ijms26157498
  20. Asatiani N, Sapojnikova N, Kartvelishvili T, Asanishvili L, Sichinava N, Chikovani Z. Blood Catalase, Superoxide Dismutase, and Glutathione Peroxidase Activities in Alcohol- and Opioid-Addicted Patients. Medicina (Mex). 2025 Feb;61(2):204. https://doi.org/10.3390/medicina61020204
  21. Qin Y, Qian C, Li W, Wang Q, Sheng Q, Chen Z, et al. Oxidative Stress: Molecular Mechanisms, Diseases, and Therapeutic Targets. MedComm. 2026 Jan 29;7(2):e70600. PubMed PMID: 41624249; PubMed Central PMCID: PMC12856066. https://doi.org/10.1002/mco2.70600
  22. Jomova K, Raptova R, Alomar SY, Alwasel SH, Nepovimova E, Kuca K, et al. Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging. Arch Toxicol. 2023;97(10):2499-574. PubMed PMID: 37597078; PubMed Central PMCID: PMC10475008. https://doi.org/10.1007/s00204-023-03562-9
  23. Didier AJ, Stiene J, Fang L, Watkins D, Dworkin LD, Creeden JF. Antioxidant and Anti-Tumor Effects of Dietary Vitamins A, C, and E. Antioxidants. 2023 Mar 3;12(3):632. PubMed PMID: 36978880; PubMed Central PMCID: PMC10045152. https://doi.org/10.3390/antiox12030632
  24. Li Z, Cao M, Yin Z, Li X, Wang Q, Dong P, et al. Functional characteristics, intercellular interactions and pathophysiological associations of astrocytes in Parkinson's disease. PeerJ. 2025 Sep 11;13:e19998. PubMed PMID: 40955304; PubMed Central PMCID: PMC12433622. https://doi.org/10.7717/peerj.19998
  25. Bolaños JP, Almeida A. Signaling roles for astrocytic lipid metabolism in brain function. EMBO Rep. 2026 Jan 3;27(3):573-80. PubMed PMID: 41484383; PubMed Central PMCID: PMC12894840. https://doi.org/10.1038/s44319-025-00683-3
  26. Zhang Y mei, Qi Y bei, Gao Y nan, Chen W gang, Zhou T, Zang Y, et al. Astrocyte metabolism and signaling pathways in the CNS. Front Neurosci. 2023 Sep 4;17:1217451. PubMed PMID: 37732313; PubMed Central PMCID: PMC10507181.https://doi.org/10.3389/fnins.2023.1217451
  27. Plascencia-Villa G, Perry G. Roles of Oxidative Stress in Synaptic Dysfunction and Neuronal Cell Death in Alzheimer's Disease. Antioxidants. 2023 Aug 17;12(8):1628. doi:10.3390/antiox12081628 PubMed PMID: 37627623; PubMed Central PMCID: PMC10451948. https://doi.org/10.3390/antiox12081628
  28. Ferdowsi S, Arjuna S, SJ S, Zennadi R. Redox Regulation of Complement Pathway Activation in Aging and Related Diseases. Antioxidants. 2025 Dec 24;15(1):29. doi:10.3390/antiox15010029 PubMed PMID: 41596089; PubMed Central PMCID: PMC12838198. https://doi.org/10.3390/antiox15010029
  29. Li Y, Tian X, Luo J, Bao T, Wang S, Wu X. Molecular mechanisms of aging and anti-aging strategies. Cell Commun Signal CCS. 2024 May 24;22:285. doi:10.1186/s12964-024-01663-1 PubMed PMID: 38790068; PubMed Central PMCID: PMC11118732. https://doi.org/10.1186/s12964-024-01663-1
  30. Weinberg SE, Chandel NS. Mitochondria reactive oxygen species signaling in immune responses. Immunity. 2025 Aug 12;58(8):1904-21. https://doi.org/10.1016/j.immuni.2025.07.012
  31. Ősz F, Nazir A, Takács-Vellai K, Farkas Z. Mutations of the Electron Transport Chain Affect Lifespan and ROS Levels in C. elegans. Antioxidants. 2025 Jan;14(1):76. https://doi.org/10.3390/antiox14010076
  32. Qiu Y, Chang S, Zeng Y, Wang X. Advances in Mitochondrial Dysfunction and Its Role in Cardiovascular Diseases. Cells. 2025 Jan;14(20):1621. https://doi.org/10.3390/cells14201621
  33. Zhang X, Gao Y, zhang S, Wang Y, Pei X, Chen Y, et al. Mitochondrial dysfunction in the regulation of aging and aging-related diseases. Cell Commun Signal CCS. 2025 Jun 19;23:290. doi:10.1186/s12964-025-02308-7 PubMed PMID: 40537801; PubMed Central PMCID: PMC12177975. https://doi.org/10.1186/s12964-025-02308-7
  34. Morciano G, Pellielo G, Agyapong ED, Pellegrino C, Patergnani S, Franceschini D, et al. The importance of mitochondria and mitochondrial calcium signaling in health and disease: an updated outlook on inflammation. J Transl Med. 2026 Feb 7;24(1):348. https://doi.org/10.1186/s12967-026-07783-1
  35. Bej E, Cesare P, d'Angelo M, Volpe AR, Castelli V. Neuronal Cell Rearrangement During Aging: Antioxidant Compounds as a Potential Therapeutic Approach. Cells. 2024 Jan;13(23):1945. https://doi.org/10.3390/cells13231945
  36. Chen TH, Wang HC, Chang CJ, Lee SY. Mitochondrial Glutathione in Cellular Redox Homeostasis and Disease Manifestation. Int J Mol Sci. 2024 Jan;25(2):1314. https://doi.org/10.3390/ijms25021314
  37. Jomova K, Alomar SY, Alwasel SH, Nepovimova E, Kuca K, Valko M. Several lines of antioxidant defense against oxidative stress: antioxidant enzymes, nanomaterials with multiple enzyme-mimicking activities, and low-molecular-weight antioxidants. Arch Toxicol. 2024;98(5):1323-67. doi:10.1007/s00204-024-03696-4 PubMed PMID: 38483584; PubMed Central PMCID: PMC11303474. https://doi.org/10.1007/s00204-024-03696-4
  38. Hammad M, Raftari M, Cesário R, Salma R, Godoy P, Emami SN, et al. Roles of Oxidative Stress and Nrf2 Signaling in Pathogenic and Non-Pathogenic Cells: A Possible General Mechanism of Resistance to Therapy. Antioxidants. 2023 Jul;12(7):1371. https://doi.org/10.3390/antiox12071371
  39. Ngo V, Duennwald ML. Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease. Antioxidants. 2022 Nov 27;11(12):2345. doi:10.3390/antiox11122345 PubMed PMID: 36552553; PubMed Central PMCID: PMC9774434. https://doi.org/10.3390/antiox11122345
  40. Perluigi M, Di Domenico F, Butterfield DA. Oxidative damage in neurodegeneration: roles in the pathogenesis and progression of Alzheimer disease. Physiol Rev. 2024 Jan;104(1):103-97. https://doi.org/10.1152/physrev.00030.2022
  41. Kozlov AV, Javadov S, Sommer N. Cellular ROS and Antioxidants: Physiological and Pathological Role. Antioxidants. 2024 May 14;13(5):602. doi:10.3390/antiox13050602 PubMed PMID: 38790707; PubMed Central PMCID: PMC11117742. https://doi.org/10.3390/antiox13050602
  42. Georgiou-Siafis SK, Tsiftsoglou AS. The Key Role of GSH in Keeping the Redox Balance in Mammalian Cells: Mechanisms and Significance of GSH in Detoxification via Formation of Conjugates. Antioxidants. 2023 Nov 1;12(11):1953. doi:10.3390/antiox12111953 PubMed PMID: 38001806; PubMed Central PMCID: PMC10669396. https://doi.org/10.3390/antiox12111953
  43. Jiang T, He Y. Recent Advances in the Role of Nuclear Factor Erythroid-2-Related Factor 2 in Spinal Cord Injury: Regulatory Mechanisms and Therapeutic Options. Front Aging Neurosci. 2022 Jun 10;14:851257. doi:10.3389/fnagi.2022.851257 PubMed PMID: 35754957; PubMed Central PMCID: PMC9226435. https://doi.org/10.3389/fnagi.2022.851257
  44. Zuo J, Zhang Z, Luo M, Zhou L, Nice EC, Zhang W, et al. Redox signaling at the crossroads of human health and disease. MedComm. 2022 Mar 31;3(2):e127. doi:10.1002/mco2.127 PubMed PMID: 35386842; PubMed Central PMCID: PMC8971743. https://doi.org/10.1002/mco2.127
  45. Rashid F, Khan KM, Saiprakash S, Ahmed G, Sultana R, Parvez F, et al. Epidemiological Evidence on the Associations of Metal Exposure with Alzheimer's Disease and Related Dementias Among Elderly Women. J Clin Med. 2025 Jan;14(11):3776. https://doi.org/10.3390/jcm14113776
  46. Hasan SK, Jayakumar S, Espina Barroso E, Jha A, Catalano G, Sandur SK, et al. Molecular Targets of Oxidative Stress: Focus on Nuclear Factor Erythroid 2-Related Factor 2 Function in Leukemia and Other Cancers. Cells. 2025 Jan;14(10):713. https://doi.org/10.3390/cells14100713
  47. Manful CF, Fordjour E, Subramaniam D, Sey AA, Abbey, Lord, Thomas R. Antioxidants and Reactive Oxygen Species: Shaping Human Health and Disease Outcomes. Int J Mol Sci. 2025 Jan;26(15):7520. https://doi.org/10.3390/ijms26157520
  48. Garcia-Llorens G, El Ouardi M, Valls-Belles V. Oxidative Stress Fundamentals: Unraveling the Pathophysiological Role of Redox Imbalance in Non-Communicable Diseases. Appl Sci. 2025 Jan;15(18):10191. https://doi.org/10.3390/app151810191
  49. Zhou Y, Manghwar H, Hu W, Liu F. Degradation Mechanism of Autophagy-Related Proteins and Research Progress. Int J Mol Sci. 2022 Jan;23(13):7301. https://doi.org/10.3390/ijms23137301
  50. Yun HR, Singh MK, Han S, Ranbhise JS, Ha J, Kim SS, et al. Roles of Autophagy and Oxidative Stress in Cardiovascular Disease. Antioxidants. 2025 Oct;14(10):1263. https://doi.org/10.3390/antiox14101263
  51. Li B, Ming H, Qin S, Nice EC, Dong J, Du Z, et al. Redox regulation: mechanisms, biology and therapeutic targets in diseases. Signal Transduct Target Ther. 2025 Mar 7;10(1):72. https://doi.org/10.1038/s41392-024-02095-6
  52. Castelli S, Aiello G, Aiello V, Massimino E, Pieri M, Amoah I, et al. Nutritional Strategies and Aging: Current Evidence and Future Directions. Molecules. 2026 Jan;31(5):756. https://doi.org/10.3390/molecules31050756
  53. Voicu V, Toader C, Șerban M, Covache-Busuioc RA, Ciurea AV. Systemic Neurodegeneration and Brain Aging: Multi-Omics Disintegration, Proteostatic Collapse, and Network Failure Across the CNS. Biomedicines. 2025 Aug;13(8):2025. https://doi.org/10.3390/biomedicines13082025
  54. Li G, Li F, Tang Y, Guo S, Yao Y, Fang Y, et al. Neurotransmitters and Immunity: Molecular Mechanisms, Biological Functions, Diseases, and Potential Therapeutic Targets. MedComm. 2025 Dec 17;6(12):e70556. doi:10.1002/mco2.70556 PubMed PMID: 41415714; PubMed Central PMCID: PMC12710542. https://doi.org/10.1002/mco2.70556
  55. Zhang T, Yin Y, Xia X, Que X, Liu X, Zhao G, et al. Regulation of synaptic function and lipid metabolism. Neural Regen Res. 2025 Apr 29;21(3):1037-57. doi:10.4103/NRR.NRR-D-24-01412 PubMed PMID: 40313084; PubMed Central PMCID: PMC12296456. https://doi.org/10.4103/NRR.NRR-D-24-01412
  56. Kim S, Jung UJ, Kim SR. Role of Oxidative Stress in Blood-Brain Barrier Disruption and Neurodegenerative Diseases. Antioxidants. 2024 Dec;13(12):1462. https://doi.org/10.3390/antiox13121462
  57. Pribicevic S, Graham AC, Cafiso DS, Pérez-Lara Á, Jahn R. Intermediate steps in the formation of neuronal SNARE complexes. J Biol Chem. 2024 Jul 19;300(8):107591. doi:10.1016/j.jbc.2024.107591 PubMed PMID: 39032647; PubMed Central PMCID: PMC11381810. https://doi.org/10.1016/j.jbc.2024.107591
  58. Jin X, Si X, Lei X, Liu H, Shao A, Li L. Disruption of Dopamine Homeostasis Associated with Alteration of Proteins in Synaptic Vesicles: A Putative Central Mechanism of Parkinson's Disease Pathogenesis. Aging Dis. 2024 May 7;15(3):1204-26. doi:10.14336/AD.2023.0821-2 PubMed PMID: 37815908; PubMed Central PMCID: PMC11081171.
  59. Tamagno WA, Freeman JL. Glutamate-Mediated Neural Alterations in Lead Exposure: Mechanisms, Pathways, and Phenotypes. Toxics. 2025 Jun 21;13(7):519. doi:10.3390/toxics13070519 PubMed PMID: 40710964; PubMed Central PMCID: PMC12300242. https://doi.org/10.3390/toxics13070519
  60. Soda T, Pasqua T, De Sarro G, Moccia F. Cognitive Impairment and Synaptic Dysfunction in Cardiovascular Disorders: The New Frontiers of the Heart-Brain Axis. Biomedicines. 2024 Oct;12(10):2387. https://doi.org/10.3390/biomedicines12102387
  61. Yang Y, Wang Q, Wang Z, Wang Y, Liu B, Zhang Y, et al. The role of fatty acids in neurodegenerative diseases: mechanistic insights and therapeutic strategies. J Lipid Res. 2025 Nov 12;66(12):100944. doi:10.1016/j.jlr.2025.100944 PubMed PMID: 41238191; PubMed Central PMCID: PMC12723386. https://doi.org/10.1016/j.jlr.2025.100944
  62. Amissah HA, Likhomanova R, Opoku G, Amissah TA, Balogi Z, Török Z, et al. Plasma Membrane Epichaperome-Lipid Interface: Regulating Dynamics and Trafficking. Cells. 2025 Jan;14(20):1582. https://doi.org/10.3390/cells14201582
  63. Gao V, Chlebowicz J, Gaskin K, Briano JA, Komer LE, Pineda A, et al. Synaptic vesicle-omics in mice captures signatures of aging and synucleinopathy. Nat Commun. 2025 May 1;16:4079. doi:10.1038/s41467-025-59441-7 PubMed PMID: 40312501; PubMed Central PMCID: PMC12046008. https://doi.org/10.1038/s41467-025-59441-7
  64. Pikor D, Hurła M, Słowikowski B, Szymanowicz O, Poszwa J, Banaszek N, et al. Calcium Ions in the Physiology and Pathology of the Central Nervous System. Int J Mol Sci. 2024 Jan;25(23):13133. https://doi.org/10.3390/ijms252313133
  65. De Nicolo B, Cataldi-Stagetti E, Diquigiovanni C, Bonora E. Calcium and Reactive Oxygen Species Signaling Interplays in Cardiac Physiology and Pathologies. Antioxidants. 2023 Feb;12(2):353. https://doi.org/10.3390/antiox12020353
  66. Wu W long, Gong X xi, Qin Z hong, Wang Y. Molecular mechanisms of excitotoxicity and their relevance to the pathogenesis of neurodegenerative diseases-an update. Acta Pharmacol Sin. 2025 Dec;46(12):3129-42. doi:10.1038/s41401-025-01576-w PubMed PMID: 40389567; PubMed Central PMCID: PMC12644896. https://doi.org/10.1038/s41401-025-01576-w
  67. Gielecińska A, Kciuk M, Kontek R. The Impact of Calcium Overload on Cellular Processes: Exploring Calcicoptosis and Its Therapeutic Potential in Cancer. Int J Mol Sci. 2024 Jan;25(24):13727. https://doi.org/10.3390/ijms252413727
  68. Duarte FV, Ciampi D, Duarte CB. Mitochondria as central hubs in synaptic modulation. Cell Mol Life Sci CMLS. 2023 Jun 2;80(6):173. doi:10.1007/s00018-023-04814-8 PubMed PMID: 37266732; PubMed Central PMCID: PMC10238361. https://doi.org/10.1007/s00018-023-04814-8
  69. Kural I, M Mombeek LM, Wilson DM. Role of mitochondria in neuronal function and survival in the enteric and central nervous systems. Cell Mol Life Sci. 2026 Feb 26;83(1):129. https://doi.org/10.1007/s00018-025-06053-5
  70. Garone C, Pietra A, Nesci S. From the Structural and (Dys)Function of ATP Synthase to Deficiency in Age-Related Diseases. Life. 2022 Mar;12(3):401. https://doi.org/10.3390/life12030401
  71. Mustaly-Kalimi S, Gallegos W, Steinbrenner D, Gupta S, Houcek AJ, Bennett DA, et al. Mitochondrial dysfunction mediated by ER-calcium dysregulation in neurons derived from Alzheimer's disease patients. Acta Neuropathol Commun. 2025 Jul 29;13:165. doi:10.1186/s40478-025-02023-x PubMed PMID: 40721842; PubMed Central PMCID: PMC12305934. https://doi.org/10.1186/s40478-025-02023-x
  72. Valiukas Z, Tangalakis K, Apostolopoulos V, Feehan J. Microglial activation states and their implications for Alzheimer's Disease. J Prev Alzheimers Dis. 2025 Jan 1;12(1):100013. https://doi.org/10.1016/j.tjpad.2024.100013
  73. Cheng XM, Hu YY, Yang T, Wu N, Wang XN. Reactive Oxygen Species and Oxidative Stress in Vascular-Related Diseases. Oxid Med Cell Longev. 2022 Apr 4;2022:7906091. doi:10.1155/2022/7906091 PubMed PMID: 35419169; PubMed Central PMCID: PMC9001081. https://doi.org/10.1155/2022/7906091
  74. Imbriani P, D'Ambra C, De Mori R, Ionta M, Renna A, Bonsi P. Dysregulation of Immune Mediators and Synaptic Plasticity in Central Nervous System Disorders. Cells. 2026 Jan;15(2):201. https://doi.org/10.3390/cells15020201
  75. Diaconescu IB, Dumitru AV, Tataru CP, Toader C, Șerban M, Covache-Busuioc RA, et al. From Electron Imbalance to Network Collapse: Decoding the Redox Code of Ischemic Stroke for Biomarker-Guided Precision Neuroprotection. Int J Mol Sci. 2025 Jan;26(22):10835.https://doi.org/10.3390/ijms262210835
  76. Meftah S, Gan J. Alzheimer's disease as a synaptopathy: Evidence for dysfunction of synapses during disease progression. Front Synaptic Neurosci. 2023 Mar 9;15:1129036. doi:10.3389/fnsyn.2023.1129036 PubMed PMID: 36970154; PubMed Central PMCID: PMC10033629. https://doi.org/10.3389/fnsyn.2023.1129036
  77. Rey F, Berardo C, Maghraby E, Mauri A, Messa L, Esposito L, et al. Redox Imbalance in Neurological Disorders in Adults and Children. Antioxidants. 2023 Apr 20;12(4):965. doi:10.3390/antiox12040965 PubMed PMID: 37107340; PubMed Central PMCID: PMC10135575. https://doi.org/10.3390/antiox12040965
  78. Velikic G, Supic G, Maric DL, Puletic M, Ovcak Kos M, Vojvodic D, et al. Neurodegeneration as Ecosystem Failure: A New Paradigm for Prevention and Treatment. Int J Mol Sci. 2025 Jan;26(22):11207. https://doi.org/10.3390/ijms262211207
  79. Tamagno E, Guglielmotto M, Vasciaveo V, Tabaton M. Oxidative Stress and Beta Amyloid in Alzheimer's Disease. Which Comes First: The Chicken or the Egg? Antioxidants. 2021 Sep 16;10(9):1479. doi:10.3390/antiox10091479 PubMed PMID: 34573112; PubMed Central PMCID: PMC8468973. https://doi.org/10.3390/antiox10091479
  80. Ali J, Choe K, Park JS, Park HY, Kang H, Park TJ, et al. The Interplay of Protein Aggregation, Genetics, and Oxidative Stress in Alzheimer's Disease: Role for Natural Antioxidants and Immunotherapeutics. Antioxidants. 2024 Jul 18;13(7):862. doi:10.3390/antiox13070862 PubMed PMID: 39061930; PubMed Central PMCID: PMC11274292. https://doi.org/10.3390/antiox13070862
  81. Jurcău MC, Andronie-Cioara FL, Jurcău A, Marcu F, Ţiț DM, Pașcalău N, et al. The Link between Oxidative Stress, Mitochondrial Dysfunction and Neuroinflammation in the Pathophysiology of Alzheimer's Disease: Therapeutic Implications and Future Perspectives. Antioxidants. 2022 Oct 31;11(11):2167. doi:10.3390/antiox11112167 PubMed PMID: 36358538; PubMed Central PMCID: PMC9686795. https://doi.org/10.3390/antiox11112167
  82. Wu YH, Hsieh HL. Effects of Redox Homeostasis and Mitochondrial Damage on Alzheimer's Disease. Antioxidants. 2023 Oct;12(10):1816. https://doi.org/10.3390/antiox12101816
  83. Wise RM, Wagener A, Fietzek UM, Klopstock T, Mosharov EV, Zucca FA, et al. Interactions of dopamine, iron, and alpha-synuclein linked to dopaminergic neuron vulnerability in Parkinson's disease and Neurodegeneration with Brain Iron Accumulation disorders. Neurobiol Dis. 2022 Dec 1;175:105920. https://doi.org/10.1016/j.nbd.2022.105920
  84. Lucchesi M, Biso L, Bonaso M, Longoni B, Buchignani B, Battini R, et al. Mitochondrial Dysfunction in Genetic and Non-Genetic Parkinson's Disease. Int J Mol Sci. 2025 Jan;26(9):4451. https://doi.org/10.3390/ijms26094451
  85. Song H, Lee J, Lee Y, Kim S, Kang S. Reactive Oxygen Species as a Common Pathological Link Between Alcohol Use Disorder and Alzheimer's Disease with Therapeutic Implications. Int J Mol Sci. 2025 Jan;26(7):3272. https://doi.org/10.3390/ijms26073272
  86. Krawczuk D, Groblewska M, Mroczko J, Winkel I, Mroczko B. The Role of α-Synuclein in Etiology of Neurodegenerative Diseases. Int J Mol Sci. 2024 Jan;25(17):9197. https://doi.org/10.3390/ijms25179197
  87. Hemerková P, Vališ M. Role of Oxidative Stress in the Pathogenesis of Amyotrophic Lateral Sclerosis: Antioxidant Metalloenzymes and Therapeutic Strategies. Biomolecules. 2021 Mar;11(3):437. https://doi.org/10.3390/biom11030437
  88. Motataianu A, Serban G, Barcutean L, Balasa R. Oxidative Stress in Amyotrophic Lateral Sclerosis: Synergy of Genetic and Environmental Factors. Int J Mol Sci. 2022 Jan;23(16):9339. https://doi.org/10.3390/ijms23169339
  89. Zhao J, Wang X, Huo Z, Chen Y, Liu J, Zhao Z, et al. The Impact of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis. Cells. 2022 Jan;11(13):2049. https://doi.org/10.3390/cells11132049
  90. Kim ME, Lim Y, Lee JS. Mitochondrial Dysfunction and Metabolic Reprogramming in Chronic Inflammatory Diseases: Molecular Insights and Therapeutic Opportunities. Curr Issues Mol Biol. 2025 Dec 14;47(12):1042. doi:10.3390/cimb47121042 PubMed PMID: 41614806; PubMed Central PMCID: PMC12731309. https://doi.org/10.3390/cimb47121042
  91. Hu C, Lin M, Wang C, Zhang S. Current Understanding of Protein Aggregation in Neurodegenerative Diseases. Int J Mol Sci. 2025 Oct 30;26(21):10568. doi:10.3390/ijms262110568 PubMed PMID: 41226604; PubMed Central PMCID: PMC12610759. https://doi.org/10.3390/ijms262110568
  92. Wu J, Wu J, Chen T, Cai J, Ren R. Protein aggregation and its affecting mechanisms in neurodegenerative diseases. Neurochem Int. 2024 Nov 1;180:105880. https://doi.org/10.1016/j.neuint.2024.105880
  93. Kumar DM, Talwar P. Amyloid-β, Tau, and α-Synuclein Protein Interactomes as Therapeutic Targets in Neurodegenerative Diseases. Cell Mol Neurobiol. 2025 Oct 6;45:84. doi:10.1007/s10571-025-01604-7 PubMed PMID: 41051722. https://doi.org/10.1007/s10571-025-01604-7
  94. Chen L, Zhang S, Liu S, Gao S. Amyotrophic Lateral Sclerosis Mechanism: Insights from the Caenorhabditis elegans Models. Cells. 2024 Jan;13(1):99. https://doi.org/10.3390/cells13010099
  95. Fan T, Peng J, Liang H, Chen W, Wang J, Xu R. Potential common pathogenesis of several neurodegenerative diseases. Neural Regen Res. 2025 May 30;21(3):972-88. doi:10.4103/NRR.NRR-D-24-01054 PubMed PMID: 40522761; PubMed Central PMCID: PMC12296512. https://doi.org/10.4103/NRR.NRR-D-24-01054
  96. Bellanti F, Coda ARD, Trecca MI, Lo Buglio A, Serviddio G, Vendemiale G. Redox Imbalance in Inflammation: The Interplay of Oxidative and Reductive Stress. Antioxidants. 2025 May 29;14(6):656. doi:10.3390/antiox14060656 PubMed PMID: 40563291; PubMed Central PMCID: PMC12189482. https://doi.org/10.3390/antiox14060656
  97. Huete-Acevedo J, Mas-Bargues C, Arnal-Forné M, Atencia-Rabadán S, Sanz-Ros J, Borrás C. Role of Redox Homeostasis in the Communication Between Brain and Liver Through Extracellular Vesicles. Antioxidants. 2024 Dec;13(12):1493. https://doi.org/10.3390/antiox13121493
  98. Hong Y, Boiti A, Vallone D, Foulkes NS. Reactive Oxygen Species Signaling and Oxidative Stress: Transcriptional Regulation and Evolution. Antioxidants. 2024 Mar;13(3):312. https://doi.org/10.3390/antiox13030312
  99. Kalogerakou T, Antoniadou M. The Role of Dietary Antioxidants, Food Supplements and Functional Foods for Energy Enhancement in Healthcare Professionals. Antioxidants. 2024 Dec;13(12):1508. https://doi.org/10.3390/antiox13121508
  100. Olaru G, Buga AM, Sandu RE, Padureanu V, Popa DG, Calina D. Harnessing Mitochondrial Function for Post-Stroke Rehabilitation: Unlocking Antioxidant Power. Antioxidants. 2025 Sep;14(9):1080. https://doi.org/10.3390/antiox14091080
  101. Narayanan K, Deviani Pakan P, Kokkinis S, Chellappan DK, Chang D, Mutalik S, et al. Emerging trends and advances in antioxidant-based plant derived nano formulations in alleviating lung diseases. J Drug Deliv Sci Technol. 2026 May 1;119:108131. https://doi.org/10.1016/j.jddst.2026.108131
  102. Poljšak B, Jamnik P, Milisav I. The Importance of Multifaceted Approach for Accurate and Comprehensive Evaluation of Oxidative Stress Status in Biological Systems. Antioxidants. 2025 Sep;14(9):1083. https://doi.org/10.3390/antiox14091083
  103. Chang KH, Chen CM. The Role of NRF2 in Trinucleotide Repeat Expansion Disorders. Antioxidants. 2024 Jun;13(6):649. https://doi.org/10.3390/antiox13060649
  104. Niziński P, Szalast K, Makuch-Kocka A, Paruch-Nosek K, Ciechanowska M, Plech T. Experimental Models and Translational Strategies in Neuroprotective Drug Development with Emphasis on Alzheimer's Disease. Molecules. 2026 Jan;31(2):320. https://doi.org/10.3390/molecules31020320
  105. Wang J, Zhang J, Zhang H, Yu F, Tian Z, Jia D. Exercise modulates redox homeostasis in cardiovascular and metabolic diseases: from bench to clinic. Cardiovasc Diabetol. 2026 Mar 14;25:127. doi:10.1186/s12933-026-03131-1 PubMed PMID: 41832545; PubMed Central PMCID: PMC13104577. https://doi.org/10.1186/s12933-026-03131-1
  106. Park MN, Choi M, Syahputra RA, Delfino DV, Ko SG, Kim B. Redox Homeostasis as a Therapeutic Target in Chronic Oxidative Diseases: Implications for Cancer Treatment. Antioxidants. 2026 Feb;15(2):203. https://doi.org/10.3390/antiox15020203
  107. Alhaj Sulaiman A, Katanaev VL. Beyond Antioxidants: How Redox Pathways Shape Cellular Signaling and Disease Outcomes. Antioxidants. 2025 Sep;14(9):1142. https://doi.org/10.3390/antiox14091142
  108. Jiang H, Zuo J, Li B, Chen R, Luo K, Xiang X, et al. Drug-induced oxidative stress in cancer treatments: Angel or devil? Redox Biol. 2023 Jul 1;63:102754. https://doi.org/10.1016/j.redox.2023.102754
  109. Ionescu C, Ghidersa M, Ciobica A, Mavroudis I, Kazis D, Petridis FE, et al. Potential Correlation Between Molecular Biomarkers and Oxidative Stress in Traumatic Brain Injury. Int J Mol Sci. 2025 Apr 18;26(8):3858. doi:10.3390/ijms26083858 PubMed PMID: 40332547; PubMed Central PMCID: PMC12027598. https://doi.org/10.3390/ijms26083858
  110. Płóciniczak A, Bukowska-Olech E, Wysocka E. The Complexity of Oxidative Stress in Human Age-Related Diseases-A Review. Metabolites. 2025 Jul;15(7):479. https://doi.org/10.3390/metabo15070479
  111. Altanam SY, Darwish N, Bakillah A. Exploring the Interplay of Antioxidants, Inflammation, and Oxidative Stress: Mechanisms, Therapeutic Potential, and Clinical Implications. Diseases. 2025 Sep;13(9):309. https://doi.org/10.3390/diseases13090309
  112. Hermann DM, Bacigaluppi M, Bassetti CL, Bassotti G, Boltze J, Chan A, et al. Most prominent challenges in translational neuroscience and strategic solutions to bridge the gaps: Perspectives from an editorial board interrogation. Explor Neurosci. 2025;4:1006106. doi:10.37349/en.2025.1006106 PubMed PMID: 40856238; PubMed Central PMCID: PMC12373390. https://doi.org/10.37349/en.2025.1006106
  113. Vo DK, Trinh KTL. Emerging Biomarkers in Metabolomics: Advancements in Precision Health and Disease Diagnosis. Int J Mol Sci. 2024 Dec 8;25(23):13190. doi:10.3390/ijms252313190 PubMed PMID: 39684900; PubMed Central PMCID: PMC11642057. https://doi.org/10.3390/ijms252313190
  114. Ren Y, Li J, Dai X. Reactive oxygen species in health and disease. Mol Biomed. 2026 Mar 13;7:30. doi:10.1186/s43556-026-00419-2 PubMed PMID: 41824175; PubMed Central PMCID: PMC12988137. https://doi.org/10.1186/s43556-026-00419-2
  115. Gogna T, Housden BE, Houldsworth A. Exploring the Role of Reactive Oxygen Species in the Pathogenesis and Pathophysiology of Alzheimer's and Parkinson's Disease and the Efficacy of Antioxidant Treatment. Antioxidants. 2024 Sep;13(9):1138. https://doi.org/10.3390/antiox13091138
  116. Rajan A, Fame RM. Brain development and bioenergetic changes. Neurobiol Dis. 2024 Sep 1;199:106550. https://doi.org/10.1016/j.nbd.2024.106550
  117. Li Pomi F, Di Leo G, Genovese S, Borgia F, Gangemi S. Redox Network Dysfunction: Integrating Ferroptosis and Cuproptosis Across Human Diseases. Antioxidants. 2026 Jan;15(1):24. https://doi.org/10.3390/antiox15010024
  118. Feelisch M, Cortese-Krott MM, Santolini J, Wootton SA, Jackson AA. Systems redox biology in health and disease. EXCLI J. 2022 Mar 21;21:623-46. doi:10.17179/excli2022-4793 PubMed PMID: 35721574; PubMed Central PMCID: PMC9203981.
  119. Lemus-Roldan K, Castorena Torres F, León Rojas D, Rodríguez-de-Ita J. From Early Adversity to Neurodegeneration: Stress Biomarkers as Predictive Signals for Lifespan Brain Health. Int J Mol Sci. 2025 Nov 14;26(22):11013. doi:10.3390/ijms262211013 PubMed PMID: 41303499; PubMed Central PMCID: PMC12652871. https://doi.org/10.3390/ijms262211013
  120. Anjo SI, He Z, Hussain Z, Farooq A, McIntyre A, Laughton CA, et al. Protein Oxidative Modifications in Neurodegenerative Diseases: From Advances in Detection and Modelling to Their Use as Disease Biomarkers. Antioxidants. 2024 Jun;13(6):681.https://doi.org/10.3390/antiox13060681

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