Format

Send to

Choose Destination
J Neural Transm (Vienna). 2011 Mar;118(3):301-14. doi: 10.1007/s00702-010-0470-z. Epub 2010 Sep 1.

Brain iron metabolism and its perturbation in neurological diseases.

Author information

1
Institute of Condensed Material and Nanosciences, Université Catholique de Louvain, Place Louis Pasteur 1, 1348, Louvain-la-Neuve, Belgium. Robert.Crichton@uclouvain.be

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.

PMID:
20809066
DOI:
10.1007/s00702-010-0470-z
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center