The role of iron in the pathogenesis of experimental allergic encephalomyelitis and multiple sclerosis.
Multiple sclerosis (MS) and its animal model, experimental allergic encephalomyelitis (EAE), are autoimmune disorders resulting in demyelination in the central nervous system (CNS). Pathologically, the blood-brain barrier becomes damaged, macrophages and T cells enter into the CNS, oligodendrocytes and myelin are destroyed, astrocytes and microglia undergo gliosis, and axons become transected. Data from several biochemical and pharmacological studies indicate that free radicals participate in the pathogenesis of EAE, and iron has been implicated as the catalyst leading to their formation. The primary focus of this article is the examination of the role of iron in the pathogenesis of MS and EAE. Particular attention will be paid to the role and distribution of iron and proteins involved with iron metabolism (e.g., transferrin, ferritin, heme oxygenase-1, etc.) in normal and disease states of myelin. Furthermore, therapeutic interventions aimed at iron, iron-binding proteins, and substrates or products of iron-catalyzed reactions leading to free radical production will be discussed.
LeVine
Steven M
SM
Department of Molecular and Integrative Physiology, Mental Retardation and Human Development Center, University of Kansas Medical Center, Kansas City 66160, USA. slevine@kumc.edu
Chakrabarty
Anuradha
A
D000818:Animals; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D005293:Ferritins / Q000378:metabolism; D005609:Free Radicals / Q000633:toxicity; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008565:Membrane Proteins; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology; D014168:Transferrin / Q000378:metabolism
D005609:Free Radicals; D008565:Membrane Proteins; D014168:Transferrin; D005293:Ferritins; D007501:Iron; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1