The Role of Iron Homeostasis in Multiple Sclerosis

Multiple sclerosis (MS) is a chronic neuroinflammatory disease characterized by demyelination, neurodegeneration, and oxidative stress. Iron dysregulation plays a critical role in MS pathology, particularly within microglia and oligodendrocytes, contributing to neuronal damage through reactive oxygen species (ROS) production. This review explores the mechanisms by which iron accumulation exacerbates oxidative stress, mitochondrial dysfunction, and neuroinflammation, leading to disease progression. The Fenton reaction, lipid peroxidation, and blood-brain barrier (BBB) disruption are key pathways through which iron-mediated damage occurs. Furthermore, the role of iron in axonal degeneration, oligodendrocyte injury, and impaired myelin repair is discussed. Potential therapeutic strategies targeting iron-induced oxidative damage include iron chelation therapy and antioxidant approaches. Iron chelators such as deferoxamine and deferasirox have shown potential in reducing oxidative stress and inflammation, although clinical outcomes remain inconclusive. Additionally, antioxidants like glutathione, coenzyme Q10, and vitamins C and E may help neutralize ROS and protect against neuronal injury; however, their efficacy in MS treatment requires further investigation. Understanding the interplay between iron homeostasis, oxidative stress, and neurodegeneration in MS is essential for developing targeted therapies that can mitigate disease progression. Future research should focus on optimizing iron-modulating treatments and identifying biomarkers to improve therapeutic outcomes.