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Iron in multiple sclerosis: roles in neurodegeneration and repair

Erin Stephenson1, Nabeela Nathoo1, Yasamin Mahjoub1

  • 1Hotchkiss Brain Institute and the Department of Clinical Neurosciences, University of Calgary, Health Medical Research Centre, Room 187, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada.

Nature Reviews. Neurology
|July 9, 2014
PubMed

Insights

Iron levels in the brain change in multiple sclerosis (MS). While excess iron can be toxic, it is also vital for myelin repair and oligodendrocyte regeneration in the central nervous system (CNS).

Area of Science:

  • Neuroscience
  • Neuroimmunology
  • Biochemistry

Background:

  • Multiple sclerosis (MS) involves global alterations in brain iron levels, particularly increased iron in macrophages and microglia.
  • Accumulated iron in MS is often considered detrimental due to its potential toxicity.
  • However, iron is crucial for oligodendrocyte and myelin integrity and regeneration after injury.

Purpose of the Study:

  • To review histological and MRI studies on iron distribution changes in MS.
  • To discuss iron sources, regulatory proteins, and the dual role of iron in the central nervous system (CNS).
  • To explore therapeutic strategies targeting iron in MS, balancing its beneficial and toxic effects.

Main Methods:

  • Review of key histological studies investigating iron distribution in MS.
  • Analysis of magnetic resonance imaging (MRI) studies examining iron levels in MS brains.
  • Discussion of cellular and molecular mechanisms of iron regulation and function in the CNS.

Main Results:

  • MS brains exhibit altered iron distribution, with increased iron in specific glial cells.
  • Excessive iron can be toxic, but iron is essential for oligodendrocyte function, myelination, and repair.
  • The extracellular matrix may play a role in modulating iron levels and remyelination.

Conclusions:

  • Iron plays a complex, dual role in MS, being both essential for repair and potentially toxic in excess.
  • Therapeutic strategies for MS should aim to modulate iron levels, supporting remyelination while preventing iron-induced damage.
  • Balancing iron homeostasis is critical for promoting CNS repair and mitigating disease progression in multiple sclerosis.

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