Dangerous Relationships: Oxidative Stress and Neuroinflammation
Dangerous Relationships: Oxidative Stress and Neuroinflammation
Keywords:
Neurodegeneración, células gliales, radicales libre, citocinasAbstract
Oxidative stress and neuroinflammation are complex biological processes that contribute to the development of neurodegenerative diseases. Oxidative stress occurs when the generation of free radicals, such as reactive oxygen species (ROS), exceeds the body antioxidant capacity. Cellular metabolism, especially during respiration and ATP synthesis at the mitochondrial level, continuously generates free radicals, making the brain particularly susceptible to oxidative stress due to its high energy demand. Neurodegenerative diseases can develop silently for years before clear signs or symptoms appear.
Neuroinflammation, on the other hand, is an immune response that is initially adaptative and attempts to restore brain homeostasis, but its chronic persistence is maladaptive and can cause neuronal damage. Glial cells, such as microglia and astrocytes, play a crucial role in producing inflammatory mediators. The prolonged activation of these cells triggers cycles of oxidative stress and neuroinflammation that feedback and amplify each other, contributing to tissue damage and neurodegeneration.
Thus, current neuroscience research is exploring protective therapeutic alternatives that include natural or synthetic compounds with antioxidant or antiinflammatory properties to prevent or mitigate the damage and reduce the progression of neurodegeneration.
References
Bernaus, A., Blanco, S., y Sevilla, A. (2020). Glia Crosstalk in Neuroinflammatory Diseases.Frontiers in Cellular Neuroscience 14:209. https://doi.org/10.3389/fncel.2020.00209
Correia, B., Fernandes, J., Botica, M., Ferreira, C., y Quintas, A. (2022). Novel Psychoactive Substances: The Razor's Edge between Therapeutical Potential and Psychoactive Recreational Misuse. Medicines (Basel) 9:19. https://doi.org/10.3390/medicines9030019.
de Fraga, L., Tassinari, I., Jantsch, J., Guedes, R., y Bambini-Junior, V. (2021). A Picture is Worth a Thousand Words: The Use of Microscopy for Imaging Neuroinflammation. Clinical Experimental Immunology 206:325. https://doi.org/10.1111/cei.13669.
Fan, Y.-Y., y Huo, J. (2021). A1/A2 Astrocytes In Central Nervous System Injuries and Diseases: Angels Or Devils? Neurochemistry International, 148: 105080. https://doi.org/10.1016/j.neuint.2021.105080.
Gao, C., Jiang, J., Tan, Y., y Chen, S. (2023), Microglia in Neurodegenerative Diseases: Mechanism and Potential Therapeutic Targets. Signal Transduction and Targeted Therapy 8:359. https://doi.org/10.1038/s41392-023-01588-0.
Halliwell, B. (2022). Reactive Oxygen Species (ROS), Oxygen Radicals and Antioxidants: Where are We Now, Where is the Field Going and Where Should We Go? Biochemical and Biophysical Research Communications 633:17. https://doi.org/10.1016/j.bbrc.2022.08.098.
Han, V. X., Patel, S., Jones, H. F., Nielsen, T.C., Mohammad, S.S., Hofer, M. J., Gold, W., Brilot, F., Lain, S. J., Nassar, N., y Dale, R. C. (2021), Maternal acute and chronic inflammation in pregnancy is associated with common neurodevelopmental disorders: a systematic review. Translational Psychiatry. 11(1):71. https://doi.org/10.1038/s41398-021-01198-w.
Jomova, K., Raptova, R., Alomar, S., Alwasel, S., Nepovimova, E., Kuca, K., y Valko, M. (20239. Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging. Archives of Toxicology 97:2499. https://doi.org/10.1007/s00204-023-03562-9.
Krishnamurthy, H.K., Pereira, M., Rajavelu, I., Jayaraman, V., Krishna, K., Wang, T., Bei, K., y Rajasekaran, J.J. Oxidative stress: fundamentals and advances in quantification techniques. Frontiers in Chemistry 12:1470458. https://doi: 10.3389/fchem.2024.1470458.
Lawrence, J., Schardien, K., Wigdahl, B., y Nonnemacher, M. (2023). Roles of Neuropathology-associated Reactive Astrocytes: A Systematic Review. Acta Neuropathologica Communications 11:42. https://doi.org/10.1186/s40478-023-01526-9.
Li, K., Geng, Y., Lin, B., y Xi, Z. (2023). Molecular Mechanisms Underlying Mitochondrial Damage, Endoplasmic Reticulum Stress, And Oxidative Stress Induced by Environmental Pollutants. Toxicology Research (Camb) 12:1014. https://doi.org/10.1093/toxres/tfad094.
Liddelow, S., Guttenplan, K., Clarke, L., Bennett, F., Bohlen, C., Schirmer, L., et al. Neurotoxic Reactive Astrocytes Are Induced by Activated Microglia. Nature 541:481. https://doi.org/10.1038/nature21029.
Loh, J., Mak, W., Tan, L., Ng, C., Chan, H, Yeow, S., Foo, J., Ong, Y., How, C., y Khaw, K. (2024). Microbiota-gut-brain Axis and Its Therapeutic Applications in Neurodegenerative Diseases. Signal Transduction and Targeted Therapy 9:37. https://doi.org/10.1038/s41392-024-01743-1.
Lomeli-Lepe A.K., Castañeda-Cabral J.L., Ureña-Guerrero M.E., Gudiño-Cabrera G., y López-Pérez S.J. (2024). Bee Venom Reduces Early Inflammation and Oxidative Stress Associated with Lipopolysaccharide-induced Alpha-synuclein in the Substantia Nigra-striatum Axis. Cell Biochemistry and Biophysics 83:1185. https://doi.org/10.1007/s12013-024-01552-x
Millichap, L., Damiani, E., Tiano, L., y Hargreaves, I. (2021). Targetable Pathways for Alleviating Mitochondrial Dysfunction in Neurodegeneration of Metabolic and Non-Metabolic Diseases. International Journal of Molecular Science 22:11444. https://doi.org/10.3390/ijms222111444.
Mohammad, Z., Yudin, S., Goldberg, B., Serra, K., Klegeris, A. (2024). Exploring Neuroglial Signaling: Diversity of Molecules Implicated in Microglia-To-Astrocyte Neuroimmune Communication. Reviews in Neuroscience 36:917. https://doi.org/10.1515/revneuro-2024-0081
Ruelas-Montes C.A. (2024) Efectos del extracto de Hibiscus sabdariffa sobre los niveles de TNF-α, IL-1β e IL-6 en la corteza prefrontal y el hipocampo de ratas macho con hiperglucemia. Tesis de Licenciatura, Universidad de Guadalajara.
Santiago, J., Karthikeyan, M., Lackey, M., Villavicencio, D., y Potashkin, J. (2023). Diabetes: A Tipping Point in Neurodegenerative Diseases. Trends in Molecular Medicine 29:1029. https://doi.org/10.1016/j.molmed.2023.09.005.
Watts, M., Pocock, R., y Claudianos, C. (2018). Brain Energy and Oxygen Metabolism: Emerging Role in Normal Function and Disease. Frontiers in Molecular Neuroscience 11:216. https://doi.org/10.3389/fnmol.2018.00216.
Xu, X., Pang, Y., y Fan, X. Mitochondria in oxidative stress, inflammation and aging: from mechanisms to therapeutic advances. Signal Transduction and Targeted Therapy, 10:190. https://doi.org/10.1038/s41392-025-02253-4.
Zhang, Z., Zhou, H., y Zhou, J. (2021). Neuritin Inhibits Astrogliosis to Ameliorate Diabetic Cognitive Dysfunction. Journal of Molecular Endocrinology, 66:259. https://doi.org/10.1530/JME-20-0321.
Zhao, J., Zhou, Y., Zhou, C., Zhan, K., Yang, M., Wen, M., y Zhu, L. (2025). Revisiting The Critical Roles of Reactive Microglia in Traumatic Brain Injury. International Journal of Surgery 111:3942. https://doi.org/10.1097/JS9.0000000000002420.
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