Ceruloplasmin dysfunction and therapeutic potential for Parkinson disease

Authors

  • Scott Ayton PhD,

    1. Oxidation Biology Laboratory, Florey Institute for Neuroscience and Mental Health, Parkville, Victoria, Australia
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  • Peng Lei PhD,

    1. Oxidation Biology Laboratory, Florey Institute for Neuroscience and Mental Health, Parkville, Victoria, Australia
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  • James A. Duce PhD,

    1. Oxidation Biology Laboratory, Florey Institute for Neuroscience and Mental Health, Parkville, Victoria, Australia
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  • Bruce X. W. Wong PhD,

    1. Oxidation Biology Laboratory, Florey Institute for Neuroscience and Mental Health, Parkville, Victoria, Australia
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  • Amelia Sedjahtera BBMS(Hons),

    1. Oxidation Biology Laboratory, Florey Institute for Neuroscience and Mental Health, Parkville, Victoria, Australia
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  • Paul A. Adlard PhD,

    1. Synaptic Neurobiology, Florey Institute for Neuroscience and Mental Health, Parkville, Victoria, Australia
    2. Department of Pathology, University of Melbourne, Parkville, Victoria, Australia
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  • Ashley I. Bush MBBS, PhD,

    Corresponding author
    1. Department of Pathology, University of Melbourne, Parkville, Victoria, Australia
    • Oxidation Biology Laboratory, Florey Institute for Neuroscience and Mental Health, Parkville, Victoria, Australia
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  • David I. Finkelstein PhD

    1. Oxidation Biology Laboratory, Florey Institute for Neuroscience and Mental Health, Parkville, Victoria, Australia
    2. Synaptic Neurobiology, Florey Institute for Neuroscience and Mental Health, Parkville, Victoria, Australia
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Address correspondence to Dr Bush, Florey Institute of Neuroscience and Mental Health, 30 Royal Parade, University of Melbourne, Victoria 3010, Australia. E-mail: ashleyib@unimelb.edu.au

Abstract

Ceruloplasmin is an iron-export ferroxidase that is abundant in plasma and also expressed in glia. We found a ∼80% loss of ceruloplasmin ferroxidase activity in the substantia nigra of idiopathic Parkinson disease (PD) cases, which could contribute to the pro-oxidant iron accumulation that characterizes the pathology. Consistent with a role for ceruloplasmin in PD etiopathogenesis, ceruloplasmin knockout mice developed parkinsonism that was rescued by iron chelation. Additionally, peripheral infusion of ceruloplasmin attenuated neurodegeneration and nigral iron elevation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model for PD. These findings show, in principle, that intravenous ceruloplasmin may have therapeutic potential in PD. Ann Neurol 2013;73:554–559

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