Present address: Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA
Pathogenic implications of iron accumulation in multiple sclerosis
Article first published online: 11 NOV 2011
© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry
Journal of Neurochemistry
Volume 120, Issue 1, pages 7–25, January 2012
How to Cite
Williams, R., Buchheit, C. L., Berman, N. E. J. and LeVine, S. M. (2012), Pathogenic implications of iron accumulation in multiple sclerosis. Journal of Neurochemistry, 120: 7–25. doi: 10.1111/j.1471-4159.2011.07536.x
- Issue published online: 14 DEC 2011
- Article first published online: 11 NOV 2011
- Accepted manuscript online: 17 OCT 2011 10:26AM EST
- Received May 23, 2011; revised manuscript received September 8, 2011; accepted October 6, 2011.
Vol. 121, Issue 2, 326, Article first published online: 17 FEB 2012
- experimental autoimmune encephalomyelitis;
- reactive oxygen species;
- transferrin receptor
J. Neurochem. (2012) 120, 7–25.
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.