caa a22 4500 445376813 CHVBK 20180317143005.0 cr unu---uuuuu 170323e20110301xx s 000 0 eng 10.1007/s00702-010-0470-z doi (NATIONALLICENCE)springer-10.1007/s00702-010-0470-z Brain iron metabolism and its perturbation in neurological diseases [Elektronische Daten] [Robert Crichton, David Dexter, Roberta Ward] 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. Springer-Verlag, 2010 Iron homeostasis nationallicence Brain iron metabolism nationallicence Alzheimer's disease nationallicence Parkinson's disease nationallicence Metal-based neurodegeneration nationallicence Crichton Robert Institute of Condensed Material and Nanosciences, Université Catholique de Louvain, Place Louis Pasteur 1, 1348, Louvain-la-Neuve, Belgium aut Dexter David Department of Cellular and Molecular Neuroscience, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, W12 ONN, London, UK aut Ward Roberta Earth and Life Institut, Université Catholique de Louvain, Place Croix du Sud, 1348, Louvain-la-Neuve, Belgium aut Journal of Neural Transmission Springer Vienna 118/3(2011-03-01), 301-314 0300-9564 118:3<301 2011 118 702 https://doi.org/10.1007/s00702-010-0470-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00702-010-0470-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Crichton Robert Institute of Condensed Material and Nanosciences, Université Catholique de Louvain, Place Louis Pasteur 1, 1348, Louvain-la-Neuve, Belgium aut NATIONALLICENCE 700 1- Dexter David Department of Cellular and Molecular Neuroscience, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, W12 ONN, London, UK aut NATIONALLICENCE 700 1- Ward Roberta Earth and Life Institut, Université Catholique de Louvain, Place Croix du Sud, 1348, Louvain-la-Neuve, Belgium aut NATIONALLICENCE 773 0- Journal of Neural Transmission Springer Vienna 118/3(2011-03-01), 301-314 0300-9564 118:3<301 2011 118 702 Metadata rights reserved Springer special CC-BY-NC licence nationallicence SWISSBIB 445376813 BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer