title: Iron and copper in progressive demyelination--New lessons from Skogholt's disease.
abstract: The pathophysiological mechanisms of progressive demyelinating disorders including multiple sclerosis are incompletely understood. Increasing evidence indicates a role for trace metals in the progression of several neurodegenerative disorders. The study of Skogholt disease, a recently discovered demyelinating disease affecting both the central and peripheral nervous system, might shed some light on the mechanisms underlying demyelination. Cerebrospinal fluid iron and copper concentrations are about four times higher in Skogholt patients than in controls. The transit into cerebrospinal fluid of these elements from blood probably occurs in protein bound form. We hypothesize that exchangeable fractions of iron and copper are further transferred from cerebrospinal fluid into myelin, thereby contributing to the pathogenesis of demyelination. Free or weakly bound iron and copper ions may exert their toxic action on myelin by catalyzing production of oxygen radicals. Similarities to demyelinating processes in multiple sclerosis and other myelinopathies are discussed.
authors.affiliation: Department of Neurology, Innlandet Hospital Trust, Lillehammer Hospital Division, Lillehammer, Norway.
authors.forename: Klaus Thanke
authors.initials: KT
authors.lastname: Aspli
authors.affiliation: Department of Chemistry, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Trond Peder
authors.initials: TP
authors.lastname: Flaten
authors.affiliation: Department of Neurology, Division of Clinical Neurophysiology, Oslo University Hospital, Oslo, Norway; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: per.roos@ki.se.
authors.forename: Per M
authors.initials: PM
authors.lastname: Roos
authors.affiliation: Department of Neurology, Akershus University Hospital, Norway; Institute of Clinical Medicine, University of Oslo, Norway.
authors.forename: Trygve
authors.initials: T
authors.lastname: Holmøy
authors.affiliation: Innlandet Hospital Trust, Kongsvinger Hospital Division, Kongsvinger, Norway.
authors.forename: Jon H
authors.initials: JH
authors.lastname: Skogholt
authors.affiliation: Innlandet Hospital Trust, Kongsvinger Hospital Division, Kongsvinger, Norway.
authors.forename: Jan
authors.initials: J
authors.lastname: Aaseth
mesh_terms: D000328:Adult; D000368:Aged; D003300:Copper / Q000134:cerebrospinal fluid* / Q000378:metabolism; D003711:Demyelinating Diseases / Q000134:cerebrospinal fluid* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007501:Iron / Q000134:cerebrospinal fluid* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D009186:Myelin Sheath / Q000276:immunology / Q000378:metabolism*; D018384:Oxidative Stress; D015854:Up-Regulation
chemical_list: D003300:Copper; D007501:Iron
keywords: Copper; Demyelination; Iron; Multiple sclerosis; Skogholt disease