Oxidative Stress Mechanisms in Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disorder of the central nervous system characterised by demyelination and axonal injury. A growing body of evidence implicates oxidative stress as both an initiator and amplifier of disease processes. Reactive oxygen and nitrogen species generated by activated microglia, macrophages and infiltrating lymphocytes inflict lipid, protein and DNA damage, while mitochondrial dysfunction and iron deposition further exacerbate free-radical production. Impaired antioxidant defences—such as diminished activity of glutathione peroxidase and superoxide dismutase alongside compensatory increases in catalase—reflect an imbalance in redox homeostasis. This oxidative milieu sustains neuroinflammation, promotes oligodendrocyte apoptosis and contributes to neurodegeneration. Understanding the interplay between oxidative injury, immune activation and mitochondrial energy failure offers avenues for novel therapeutic strategies aimed at bolstering endogenous antioxidant capacity and mitigating progressive tissue damage.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Oxidative Stress Mechanisms in Multiple Sclerosis publication trend

The graph below shows the total number of articles in oxidative stress mechanisms in multiple sclerosis across all publications each year (not limited to Nature Index journals).

Technical terms

Oxidative stress: An imbalance between pro-oxidant species and antioxidant defences leading to cellular damage.

Reactive oxygen species (ROS): Highly reactive molecules derived from oxygen that can damage lipids, proteins and DNA.

Reactive nitrogen species (RNS): Nitrogen-derived free radicals and non-radical species that contribute to oxidative injury.

Ferroptosis: A regulated form of cell death driven by iron-dependent lipid peroxidation.

Glutathione peroxidase (GPx): An enzyme that reduces hydrogen peroxide and lipid hydroperoxides using glutathione.

Superoxide dismutase (SOD): An enzyme that converts superoxide radicals into oxygen and hydrogen peroxide.

Catalase (CAT): An enzyme that decomposes hydrogen peroxide into water and oxygen, mitigating oxidative damage.

NRF2–KEAP1 pathway: A cellular defence mechanism regulating antioxidant gene expression in response to oxidative stress.

References

1. Exploring the Relationship between Antioxidant Enzymes, Oxidative Stress Markers, and Clinical Profile in Relapsing–Remitting Multiple Sclerosis. Antioxidants (2023).
2. Circulatory Indicators of Lipid Peroxidation, the Driver of Ferroptosis, Reflect Differences between Relapsing–Remitting and Progressive Multiple Sclerosis. International Journal of Molecular Sciences (2024).
3. New Insights into the Role of Oxidative Stress Mechanisms in the Pathophysiology and Treatment of Multiple Sclerosis. Oxidative Medicine and Cellular Longevity (2016).
4. Inflammation and Oxidative Stress in Multiple Sclerosis: Consequences for Therapy Development. Oxidative Medicine and Cellular Longevity (2020).
5. Monitoring the Redox Status in Multiple Sclerosis. Biomedicines (2020).
6. Inflammation, Iron, Energy Failure, and Oxidative Stress in the Pathogenesis of Multiple Sclerosis. Oxidative Medicine and Cellular Longevity (2015).