Copper pathology in vulnerable brain regions in Parkinson’s disease

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Abstract
Synchrotron-based X-ray fluorescence microscopy, immunofluorescence, and western blotting were used to investigate changes in copper (Cu) and Cu-associated pathways in the vulnerable SN and locus coeruleus (LC), and non-degenerating brain regions, in cases of Parkinson’s disease and appropriate healthy and disease controls. In PD and incidental Lewy body disease (ILBD), levels of Cu and Cu transporter protein 1 (Ctr1), were significantly reduced in surviving neurons in the SN and LC. Specific activity of the cuproprotein superoxide dismutase 1 (SOD1) was unchanged in the SN in PD but was enhanced in the parkinsonian anterior cingulate cortex (ACC), a region with α-synuclein pathology, normal Cu and limited cell loss. These data suggest that regions affected by α-synuclein pathology may display enhanced vulnerability and cell loss if Cu-dependent protective mechanisms are compromised. Further investigation of copper pathology in PD may identify novel targets for the development of protective therapies for this disorder.
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Author(s)
Davies, Katherine M
Bohic, Sylvain
Carmona, Asunción
Ortega, Richard
Cottam, Veronica
Hare, Dominic J
Finberg, John PM
Reyes, Stephanie
Halliday, Glenda
Mercer, Julian FB
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Publication Year
2014
Resource Type
Journal Article
Degree Type
UNSW Faculty
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