title: Dysregulated iron metabolism in the choroid plexus in fragile X-associated tremor/ataxia syndrome.
abstract: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder associated with premutation alleles of the FMR1 gene that is characterized by progressive action tremor, gait ataxia, and cognitive decline. Recent studies of mitochondrial dysfunction in FXTAS have suggested that iron dysregulation may be one component of disease pathogenesis. We tested the hypothesis that iron dysregulation is part of the pathogenic process in FXTAS. We analyzed postmortem choroid plexus from FXTAS and control subjects, and found that in FXTAS iron accumulated in the stroma, transferrin levels were decreased in the epithelial cells, and transferrin receptor 1 distribution was shifted from the basolateral membrane (control) to a predominantly intracellular location (FXTAS). In addition, ferroportin and ceruloplasmin were markedly decreased within the epithelial cells. These alterations have implications not only for understanding the pathophysiology of FXTAS, but also for the development of new clinical treatments that may incorporate selective iron chelation.
authors.affiliation: Institute for Pediatric Regenerative Medicine, Shriners Hospital of Northern California, University of California, Davis, 2425 Stockton Blvd, Sacramento, CA 95817, USA; Department of Pathology and Laboratory Medicine, University of California, Davis 4400 V Street, Sacramento, CA 95817, USA.
authors.forename: Jeanelle
authors.initials: J
authors.lastname: Ariza
authors.affiliation: Institute for Pediatric Regenerative Medicine, Shriners Hospital of Northern California, University of California, Davis, 2425 Stockton Blvd, Sacramento, CA 95817, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Steward
authors.affiliation: Institute for Pediatric Regenerative Medicine, Shriners Hospital of Northern California, University of California, Davis, 2425 Stockton Blvd, Sacramento, CA 95817, USA.
authors.forename: Flora
authors.initials: F
authors.lastname: Rueckert
authors.affiliation: Institute for Pediatric Regenerative Medicine, Shriners Hospital of Northern California, University of California, Davis, 2425 Stockton Blvd, Sacramento, CA 95817, USA.
authors.forename: Matt
authors.initials: M
authors.lastname: Widdison
authors.affiliation: Institute for Pediatric Regenerative Medicine, Shriners Hospital of Northern California, University of California, Davis, 2425 Stockton Blvd, Sacramento, CA 95817, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Coffman
authors.affiliation: Institute for Pediatric Regenerative Medicine, Shriners Hospital of Northern California, University of California, Davis, 2425 Stockton Blvd, Sacramento, CA 95817, USA.
authors.forename: Atiyeh
authors.initials: A
authors.lastname: Afjei
authors.affiliation: Department of Psychiatry, University of California, Davis, 2805 50th St., Sacramento, CA 95817, USA; MIND Institute, University of California, Davis, 2825 50th Street, Sacramento, CA 95817, USA.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Noctor
authors.affiliation: MIND Institute, University of California, Davis, 2825 50th Street, Sacramento, CA 95817, USA; Department of Pediatrics, University of California, Davis, 2825 50th Street, Sacramento, CA 95817, USA.
authors.forename: Randi
authors.initials: R
authors.lastname: Hagerman
authors.affiliation: MIND Institute, University of California, Davis, 2825 50th Street, Sacramento, CA 95817, USA; Department of Biochemistry and Molecular Medicine, University of California, Davis, One Shields Avenue, CA 95616, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Hagerman
authors.affiliation: Institute for Pediatric Regenerative Medicine, Shriners Hospital of Northern California, University of California, Davis, 2425 Stockton Blvd, Sacramento, CA 95817, USA; Department of Pathology and Laboratory Medicine, University of California, Davis 4400 V Street, Sacramento, CA 95817, USA; MIND Institute, University of California, Davis, 2825 50th Street, Sacramento, CA 95817, USA. Electronic address: vmartinezcerdeno@ucdavis.edu.
authors.forename: Verónica
authors.initials: V
authors.lastname: Martínez-Cerdeño
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D001259:Ataxia / Q000378:metabolism* / Q000473:pathology; D027682:Cation Transport Proteins / Q000172:deficiency; D002570:Ceruloplasmin / Q000172:deficiency; D002831:Choroid Plexus / Q000378:metabolism* / Q000473:pathology; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D005600:Fragile X Syndrome / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011990:Receptors, Transferrin / Q000378:metabolism; D014168:Transferrin / Q000172:deficiency; D014202:Tremor / Q000378:metabolism* / Q000473:pathology; D000098742:Ferroportin
chemical_list: D015703:Antigens, CD; C068126:CD71 antigen; D027682:Cation Transport Proteins; D011990:Receptors, Transferrin; D014168:Transferrin; D000098742:Ferroportin; D007501:Iron; D002570:Ceruloplasmin
keywords: Autism; CGG repeat; Choroid plexus; FMR1; FXTAS; Fragile X; Iron; Neurodegeneration; Premutation