Journal of Neural Transmission

, Volume 118, Issue 3, pp 301–314 | Cite as

Brain iron metabolism and its perturbation in neurological diseases

  • Robert R. Crichton
  • David T. Dexter
  • Roberta J. Ward
Basic Neurosciences, Genetics and Immunology - Review article
First Online:
Received:
Accepted:

Abstract

Metal ions are of particular importance in brain function, notably iron. A broad overview of iron metabolism and its homeostasis both at the cellular level (involving regulation at the level of mRNA translation) and the systemic level (involving the peptide ‘hormone’ hepcidin) is presented. The mechanisms of iron transport both across the blood–brain barrier and within the brain are then examined. The importance of iron in the developing foetus and in early life is underlined. We then review the growing corpus of evidence that many neurodegenerative diseases (NDs) are the consequence of dysregulation of brain iron homeostasis. This results in the production of reactive oxygen species, generating reactive aldehydes, which, together with further oxidative insults, causes oxidative modification of proteins, manifested by carbonyl formation. These misfolded and damaged proteins overwhelm the ubiquitin/proteasome system, accumulating the characteristic inclusion bodies found in many NDs. The involvement of iron in Alzheimer’s disease and Parkinson’s disease is then examined, with emphasis on recent data linking in particular interactions between iron homeostasis and key disease proteins. We conclude that there is overwhelming evidence for a direct involvement of iron in NDs.

Keywords

Iron homeostasis Brain iron metabolism Alzheimer’s disease Parkinson’s disease Metal-based neurodegeneration 
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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Robert R. Crichton
    • 1
  • David T. Dexter
    • 2
  • Roberta J. Ward
    • 3
  1. 1.Institute of Condensed Material and NanosciencesUniversité Catholique de LouvainLouvain-la-NeuveBelgium
  2. 2.Department of Cellular and Molecular Neuroscience, Faculty of MedicineImperial College LondonLondonUK
  3. 3.Earth and Life InstitutUniversité Catholique de LouvainLouvain-la-NeuveBelgium

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