Iron in multiple sclerosis – from pathophysiology to disease progression – a narrative literature review

Abstract

Multiple sclerosis (MS) is a chronic autoimmune illness characterized by demyelination and neurodegeneration, which causes physical disability and severe alterations in the neurological system, including gliosis and neuron loss. The disease primarily affects myelinated parts of the central nervous system (CNS), such as the optic nerves, cerebellum, brain stem, and spinal cord. T cells play an important role in MS pathogenesis by inducing demyelination, and risk factors include genetic predisposition, environmental effects, and lifestyle decisions. The prevalence of MS is rising, especially among women and the elderly population. Iron dysregulation is a critical element in MS pathogenesis, with excess iron causing neurodegeneration via ferroptosis and immune response modulation. Excess iron amplifies inflammation by triggering the activation of macrophages with inflammatory properties, and promoting microglial polarization toward the pro‑inflammatory phenotype. This causes increased oxidative stress, mitochondrial malfunction, and the release of reactive oxygen species, which harm neurons. Furthermore, proinflammatory cytokines like IL‑6 regulate iron metabolism and encourage the formation of Th17 cells, which exacerbates CNS inflammation. Macrophages and microglia, which are implicated in inflammatory responses, collect iron during MS, exacerbating neuroinflammation and demyelination. Disrupted iron homeostasis is a major contributor to MS pathology, with iron deficiency affecting immunological function and changing T‑cell responses, both of which are necessary for disease progression. Lumbar puncture, oligoclonal bands analysis, and magnetic resonance imaging are all used to diagnose MS and confirm disease activity and progression. The blood‑brain barrier is frequently disrupted in MS, allowing the influx of inflammatory cells. The aim of this paper is to demonstrate the cause‑effect relationship between the amount of iron and the health status of patients with MS.