Copper pathology in vulnerable brain regions in Parkinson's disease
Open accessAbstract
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 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. Additional investigation of copper pathology in PD may identify novel targets for the development of protective therapies for this disorder.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In plaques from persons with Alzheimer's disease, iron and aluminum appear to cause plaque formation while copper and zinc may be protective.
“In plaques from persons with Alzheimer’s disease, iron and aluminum appear to cause plaque formation while copper and zinc may be protective [26,27,28,35,36,37].”
From The Effect of the Human Peptide GHK on Gene Expression Relevant to Nervous System Function and Cognitive Decline (2017) · cites this paper as [36]
Cites
Hyman, B. T., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Carrillo, M. C., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., et al. (2012) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.10.007 · Cited by 3,092 · see citing works
Montine, T. J., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., Mirra, S. S., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-011-0910-3 · Cited by 2,992 · cited 3× · see citing works
“…Lewy Body disease (ILBD), identified according to the diagnostic criteria of Dickson et al. (Dickson et al., 2009), and from Alzheimer’s disease (AD) and age-matched controls, identified according to the diagnostic criteria of Montine et al. (Montine et al., 2012) (Supplementary Tables 1, 2 and 3).”
MethodMelanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease
Hirsch, E., Graybiel, A. M., & Agid, Y. A. (1988) · Nature · doi:10.1038/334345a0 · Cited by 1,301 · cited 2× · see citing works
“, 2008), an intracellular pigment found in vulnerable regions of the PD brain (Hirsch et al., 1988).”
BackgroundDexter, D. T., Wells, F. R., Lee, A. J., Agid, F., Agid, Y., Jenner, P., & Marsden, C. D. (1989) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1989.tb07264.x · Cited by 1,149 · see citing works
Ceruloplasmin dysfunction and therapeutic potential for Parkinson disease
Ayton, S., Lei, P., Duce, J. A., Wong, B. X. W., Sedjahtera, A., Adlard, P. A., Bush, A. I., & Finkelstein, D. I. (2013) · Annals of Neurology · doi:10.1002/ana.23817 · Cited by 264 · see citing works
Antharam, V., Collingwood, J. F., Bullivant, J.-P., Davidson, M. R., Chandra, S., Mikhaylova, A., Finnegan, M. E., Batich, C., Forder, J. R., & Dobson, J. (2012) · NeuroImage · doi:10.1016/j.neuroimage.2011.08.019 · Cited by 82 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Neuron-Astrocyte Interactions in Parkinson’s Disease
Miyazaki, I., & Asanuma, M. (2020) · Cells · doi:10.3390/cells9122623 · Cited by 186 · see citing works
Vasquez, V., Mitra, J., Hegde, P. M., Pandey, A., Sengupta, S., Mitra, S., Rao, K. S., & Hegde, M. L. (2017) · Journal of Alzheimer's Disease · doi:10.3233/jad-170342 · Cited by 88 · see citing works
Pickart, L., Vasquez-Soltero, J., & Margolina, A. (2017) · Brain Sciences · doi:10.3390/brainsci7020020 · Cited by 51 · see citing works
Iron Redox Chemistry and Implications in the Parkinson’s Disease Brain
Abeyawardhane, D. L., & Lucas, H. R. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/4609702 · Cited by 35 · see citing works
- Authors
- Davies, K. M., Bohic, S., Carmona, A., Ortega, R., Cottam, V., Hare, D. J., Finberg, J. P. M., Reyes, S., Halliday, G. M., Mercer, J. F. B., & Double, K. L.
- Affiliations
- UNSW Sydney (AU)
- Inserm (FR)
- Centre National de la Recherche Scientifique (FR)
- Neuroscience Research Australia (AU)
- University of Technology Sydney (AU)
- Technion – Israel Institute of Technology (IL)
- Deakin University (AU)
- The University of Sydney (AU)
- Corresponding author
- Bohic, Sylvain
- Double, Kay L.
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2014-04
- Volume
- 35
- Issue
- 4
- Pages
- 858-866
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2061177324
- Cited by
- 244
- References
- 6
- Citations by year
- 2026: 14 · 2025: 16 · 2024: 18 · 2023: 11 · 2022: 17 · 2021: 13 · 2020: 21 · 2019: 43 · 2018: 22 · 2017: 30 · 2016: 14 · 2015: 15 · 2014: 10
- FWCI
- 8.26
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
- UNSWorks (UNSW Sydney) (submittedVersion, cc-by-nc-nd)
- HAL (submittedVersion, other-oa)
- UTS ePRESS (University of Technology Sydney) (submittedVersion)
- Oskar-Bordeaux (Universite de Bordeaux) (submittedVersion)
- Funders
- National Health and Medical Research Council
- Schizophrenia Research Institute
- National Institute of Alcohol Abuse and Alcoholism (R24AA012725)
- Sydney Brain Bank
- Neuroscience Research Australia
- University of New South Wales
- National Health and Medical Research Council of Australia
- Partenariats Hubert Curien
- Australian Department of Innovatio
- Industry
- Science and Research International Science Linkage FAST programs
- Parkinson's New South Wales
- Parkinson's Australia Capital Territory
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- Parkinson's disease, copper, CTR1, superoxide dismutase 1, substantia nigra, locus coeruleus, alpha-synuclein, Lewy body disease, anterior cingulate cortex, neuronal vulnerability, neurodegeneration, synchrotron X-ray fluorescence microscopy
- MeSH terms
- Superoxide Dismutase-1, Copper Transporter 1, Copper, Gyrus Cinguli, Humans, Locus Coeruleus, Neurons, Parkinson Disease, Substantia Nigra, Superoxide Dismutase, Cation Transport Proteins, alpha-Synuclein, Molecular Targeted Therapy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
