title: Copper dyshomoeostasis in Parkinson's disease: implications for pathogenesis and indications for novel therapeutics.
abstract: Copper is a biometal essential for normal brain development and function, thus copper deficiency or excess results in central nervous system disease. Well-characterized disorders of disrupted copper homoeostasis with neuronal degeneration include Menkes disease and Wilson's disease but a large body of evidence also implicates disrupted copper pathways in other neurodegenerative disorders, including Parkinson's disease, Alzheimer's disease, Amyotrophic lateral sclerosis, Huntington's disease and prion diseases. In this short review we critically evaluate the data regarding changes in systemic and brain copper levels in Parkinson's disease, where alterations in brain copper are associated with regional neuronal cell death and disease pathology. We review copper regulating mechanisms in the human brain and the effects of dysfunction within these systems. We then examine the evidence for a role for copper in pathogenic processes in Parkinson's disease and consider reports of diverse copper-modulating strategies in in vitro and in vivo models of this disorder. Copper-modulating therapies are currently advancing through clinical trials for Alzheimer's and Huntington's disease and may also hold promise as disease modifying agents in Parkinson's disease.
authors.affiliation: Neuroscience Research Australia, Sydney, NSW 2031, Australia School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Davies
authors.affiliation: Centre for Cellular and Molecular Biology, School of Life and Environmental Sciences, Deakin University, Melbourne, VIC 3125, Australia.
authors.forename: Julian F B
authors.initials: JF
authors.lastname: Mercer
authors.affiliation: Neuroscience Research Australia, Sydney, NSW 2031, Australia.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Chen
authors.affiliation: Brain and Mind Centre and Discipline of Biomedical Sciences, School of Medical Sciences, Sydney Medical School, The University of Sydney, Sydney, NSW 2050, Australia kay.double@sydney.edu.au.
authors.forename: Kay L
authors.initials: KL
authors.lastname: Double
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003300:Copper / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D000978:Antiparkinson Agents; D051844:alpha-Synuclein; D003300:Copper
keywords: Parkinson's disease; brain; copper; homoeostasis; neurodegeneration; therapy