Pathogenic implications of iron accumulation in multiple sclerosis

Authors

  • Rachel Williams,

    1. Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, USA
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  • Cassandra L. Buchheit,

    1. Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, USA
    2. Biochemistry Program, Rockhurst University, Kansas City, Missouri, USA
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    • Present address: Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA

  • Nancy E. J. Berman,

    1. Department of Anatomy & Cell Biology, University of Kansas Medical Center, Kansas City, Kansas, USA
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  • Steven M. LeVine

    1. Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, USA
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Errata

This article is corrected by:

  1. Errata: Erratum Volume 121, Issue 2, 326, Article first published online: 17 February 2012

Address correspondence and reprint requests to Steven LeVine, PhD, Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Blvd. Mail Stop 3043, Kansas City, KS 66160, USA. E-mail: slevine@kumc.edu

Abstract

J. Neurochem. (2012) 120, 7–25.

Abstract

Iron, an essential element used for a multitude of biochemical reactions, abnormally accumulates in the CNS of patients with multiple sclerosis (MS). The mechanisms of abnormal iron deposition in MS are not fully understood, nor do we know whether these deposits have adverse consequences, that is, contribute to pathogenesis. With some exceptions, excess levels of iron are represented concomitantly in multiple deep gray matter structures often with bilateral representation, whereas in white matter, pathological iron deposits are usually located at sites of inflammation that are associated with veins. These distinct spatial patterns suggest disparate mechanisms of iron accumulation between these regions. Iron has been postulated to promote disease activity in MS by various means: (i) iron can amplify the activated state of microglia resulting in the increased production of proinflammatory mediators; (ii) excess intracellular iron deposits could promote mitochondria dysfunction; and (iii) improperly managed iron could catalyze the production of damaging reactive oxygen species (ROS). The pathological consequences of abnormal iron deposits may be dependent on the affected brain region and/or accumulation process. Here, we review putative mechanisms of enhanced iron uptake in MS and address the likely roles of iron in the pathogenesis of this disease.

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