Copper and iron changes in Parkinson's disease brain; implications for aetiology and potential for novel treatments

Abstract

Event Abstract Back to Event Copper and iron changes in Parkinson's disease brain; implications for aetiology and potential for novel treatments Katherine Davies1, Benjamin Trist2, Veronica Cottam2, Dominic J. Hare3, Sylvain Bohic4, Asuncion Carmona5, Richard Ortega5 and Kay L. Double2* 1 Neuroscience Research Australia, Australia 2 The University of Sydney, School of Medical Sciences, Sydney Medical School, Australia 3 Florey Institute of Neuroscience and Mental Health, University of Technology Sydney, and The University of Melbourne , Australia 4 Universite Grenoble Alpes, Inserm, France 5 and Centre National de la Recherche Scientifique, University of Bordeaux, France We have used sensitive, high resolution biophysical imaging methods to investigate biometals changes at the single cell level in the Parkinson’s disease brain. Consistent with a large body of bulk tissue reports, we identified increased intraneuronal Fe in the degenerating substantia nigra in this disorder, a change not present in non-degenerating brain regions. We have suggested that Fe and dopamine form a potent biochemical redox couple, thus the accumulation of Fe within the dopaminergic substantia nigra in the Parkinson’s disease brain may contribute to the selective vulnerability of this brain region. We also identified significantly decreased Cu levels in these same neurons, associated with altered cellular Cu transport pathways. Decreased intraneuronal Cu was also present in the substantia nigra in incidental Lewy body disease prior to the onset of neuronal loss, suggesting this change occurs early in the disease process. The decrease in Cu in these vulnerable neurons is associated with alterations in cuproproteins. Regional changes in cuproproteins in the Parkinson’s disease brain may contribute to the accumulation of intraneuronal Fe in this disorder, but also to mechanisms of degeneration linked to dysfunction of the cuproprotein superoxide dismutase 1. We suggest that normalisation of brain Fe and Cu levels in Parkinson’s disease brain represents a tractable target for neuroprotective therapy. Keywords: Copper, Iron, Substantia Nigra, Parkinson, neurodegeneration Conference: 14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016. Presentation Type: Symposium 3: Metals in the Aetiology and Treatment of Neurodegenerative Diseases Topic: 14th Meeting of the Asian-Pacific Society for Neurochemistry Citation: Davies K, Trist B, Cottam V, Hare DJ, Bohic S, Carmona A, Ortega R and Double KL (2016). Copper and iron changes in Parkinson's disease brain; implications for aetiology and potential for novel treatments. Conference Abstract: 14th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00015 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 26 Jul 2016; Published Online: 11 Aug 2016. * Correspondence: Prof. Kay L Double, The University of Sydney, School of Medical Sciences, Sydney Medical School, Sydney, NSW, Australia, kay.double@sydney.edu.au Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Katherine Davies Benjamin Trist Veronica Cottam Dominic J Hare Sylvain Bohic Asuncion Carmona Richard Ortega Kay L Double Google Katherine Davies Benjamin Trist Veronica Cottam Dominic J Hare Sylvain Bohic Asuncion Carmona Richard Ortega Kay L Double Google Scholar Katherine Davies Benjamin Trist Veronica Cottam Dominic J Hare Sylvain Bohic Asuncion Carmona Richard Ortega Kay L Double PubMed Katherine Davies Benjamin Trist Veronica Cottam Dominic J Hare Sylvain Bohic Asuncion Carmona Richard Ortega Kay L Double Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.