As with most bioavailable transition metals, iron is essential for many metabolic processes required by the cell but when left unregulated is implicated as a potent source of reactive oxygen species. It is uncertain whether the brain’s evident vulnerability to reactive species-induced oxidative stress is caused by a reduced capability in cellular response or an increased metabolic activity. Either way, dys-regulated iron levels appear to be involved in oxidative stress provoked neurodegeneration. As in peripheral iron management, cells within the central nervous system tightly regulate iron homeostasis via responsive expression of select proteins required for iron flux, transport and storage. Recently proteins directly implicated in the most prevalent neurodegenerative diseases, such as amyloid-β precursor protein, tau, α-synuclein, prion protein and huntingtin, have been connected to neuronal iron homeostatic control. This suggests that disrupted expression, processing, or location of these proteins may result in a failure of their cellular iron homeostatic roles and augment the common underlying susceptibility to neuronal oxidative damage that is triggered in neurodegenerative disease.
Keywords: Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, prion disease, amyloid-β precursor protein, tau, α-synuclein, prion protein
Citation: Wong BX and Duce JA (2014) The iron regulatory capability of the major protein participants in prevalent neurodegenerative disorders. Front. Pharmacol. 5:81. doi: 10.3389/fphar.2014.00081
Received: 28 February 2014; Paper pending published: 08 March 2014;
Accepted: 02 April 2014; Published online: 21 April 2014.
Edited by:Raffaella Gozzelino, Instituto Gulbenkian de Ciência, Portugal
Reviewed by:Dominic James Hare, University of Technology at Sydney, Australia
Copyright © 2014 Wong and Duce. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: James A. Duce, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK e-mail: email@example.com