Abstract
MRI and histological studies have shown global alterations in iron levels in the brains of patients with
multiple sclerosis (MS), including increases in the iron stored by macrophages and microglia. Excessive free
iron can be toxic, and accumulation of iron in MS has generally been thought to be detrimental. However, iron
maintains the integrity of oligodendrocytes and myelin, and facilitates their regeneration following injury. The
extracellular matrix, a key regulator of remyelination, might also modulate iron levels. This Review highlights key
histological and MRI studies that have investigated changes in iron distribution associated with MS. Potential
sources of iron, as well as iron regulatory proteins and the detrimental roles of excessive iron within the CNS,
are also discussed, with emphasis on the importance of iron within cells for oxidative metabolism, proliferation
and differentiation of oligodendrocytes, and myelination. In light of the beneficial and detrimental properties
of iron within the CNS, we present considerations for treatments that target iron in MS. Such treatments must
balance trophic and toxic properties of iron, by providing sufficient iron levels for remyelination and repair while
avoiding excesses that might overwhelm homeostatic mechanisms and contribute to damage.
Grantingagency
Canadian Institutes of Health Research; Multiple Sclerosis Society of Canada; Alberta Innovates–Health Solutions CRIO Team programme
Refereed
Yes
