Copper pathology in vulnerable brain regions in Parkinson's disease

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• 作者：Katherine M. Davies ; Sylvain Bohic ; Asunci贸n Carmona ; Richard Ortega ; Veronica Cottam ; Dominic J. Hare ; John P.M. Finberg ; Stefanie Reyes ; Glenda M. Halliday ; Julian F.B. Mercer ; Kay L. Double
• 关键词：Copper ; Copper transporter 1 (Ctr1) ; Human brain ; Parkinson's disease ; Substantia nigra ; Superoxide dismutase 1 (SOD1)
• 刊名：Neurobiology of Aging
• 出版年：April, 2014
• 年：2014
• 卷：35
• 期：4
• 页码：858-866
• 全文大小：1832 K

文摘

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 substantia nigra (SN) and locus coeruleus (LC) and in nondegenerating brain regions in cases of Parkinson's disease (PD) and appropriate healthy and disease controls. In PD and incidental Lewy body disease, levels of Cu and Cu transporter protein 1, were significantly reduced in surviving neurons in the SN and LC. Specific activity of the cuproprotein superoxide dismutase 1 was unchanged in the SN in PD but was enhanced in the parkinsonian anterior cingulate cortex, a region with 伪-synuclein pathology, normal Cu, and limited cell loss. These data suggest that regions affected by 伪-synuclein pathology may display enhanced vulnerability and cell loss if Cu-dependent protective mechanisms are compromised. Additional investigation of copper pathology in PD may identify novel targets for the development of protective therapies for this disorder.