Brain iron disorders

doi:10.1017/CBO9780511544873.061

60 - Brain iron disorders

from Part X - Other neurodegenerative diseases

Published online by Cambridge University Press: 04 August 2010

Anthony E. Lang and

Hiroaki Miyajima and

M. Flint Beal: Affiliation:
Cornell University, New York
Anthony E. Lang: Affiliation:
University of Toronto
Albert C. Ludolph: Affiliation:
Universität Ulm, Germany
Satoshi Kono: Affiliation:
Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
Hiroaki Miyajima: Affiliation:
First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
Jonathan D. Gitlin: Affiliation:
Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA

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Summary

Introduction

Iron is an essential transition metal required for the binding and activation of dioxygen in a series of critical transport and redox reactions. The facile electron chemistry of iron also accounts for the toxicity of this metal and therefore intricate pathways have evolved to allow for the transport, trafficking and compartmentalization of iron within cells (Kaplan, 2002a). These pathways prevent the formation of iron-induced reactive oxygen intermediates that contribute to the pathogenesis of tissue injury in inherited disorders of iron homeostasis such as hemochromatosis with resultant cirrhosis, diabetes and cardiac failure (Lee et al., 2002). Within the central nervous system, iron is required for critical, diverse processes including neurotransmitter biosynthesis, myelin formation and nitric oxide signaling, as well as oxidative phosphorylation essential for sustaining brain energy requirements (Sipe et al., 2002). Despite this critical role of iron in brain function, the molecular and cellular details of iron metabolism within the human central nervous system remain poorly understood.

Iron uptake into the brain is dependent upon plasma transferrin and transferrin receptors localized to the microvasculature. Although both the apical membrane divalent iron transporter DMT1 and the basolateral transporter ferroportin are expressed within the central nervous system, the precise role of these proteins in brain iron homeostasis is currently unknown (Sipe et al., 2002). The intracellular iron binding protein ferritin is abundantly expressed in neurons and glia and presumably serves as the major source of iron storage within these cells.

Type: Chapter
Information: Neurodegenerative Diseases
Neurobiology, Pathogenesis and Therapeutics
, pp. 880 - 889

DOI: https://doi.org/10.1017/CBO9780511544873.061 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2005

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