The Role of Copper in Neurodegenerative Disease

Waggoner, Darrel; Bartnikas, Thomas B.; Gitlin, Jonathan D.

doi:10.1006/nbdi.1999.0250

Cited by 807 publications

(453 citation statements)

References 92 publications

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“…There is also evidence from Prnpdeficient mice that their cerebellar cells have an increased sensitivity to the toxicity of copper-containing salts (29), a marked decrease in membrane copper content, and decreased activity of superoxide dismutase 1 (30,31), suggesting that the prion protein may play a role in copper homeostasis in the CNS. The role of copper in other neurodegenerative diseases raises the possibility of a common neurodegenerative process linked to copper homeostasis and transport (32).…”

Section: Discussionmentioning

confidence: 99%

Genetic and environmental factors modify bovine spongiform encephalopathy incubation period in mice

Manolakou

Beaton

McConnell

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

114

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The incubation period (IP) and the neuropathology of transmissible spongiform encephalopathies (TSEs) have been extensively used to distinguish prion isolates (or strains) inoculated into panels of inbred mouse strains. Such studies have shown that the bovine spongiform encephalopathy (BSE) agent is indistinguishable from the agent causing variant Creutzfeldt-Jakob disease (vCJD), but differs from isolates of sporadic CJD, reinforcing the idea that the vCJD epidemic in Britain results from consumption of contaminated beef products. We present a mouse model for genetic and environmental factors that modify the incubation period of BSE crossspecies transmission. We have used two mouse strains that carry the same prion protein (PrP) allele, but display a 100-day difference in their mean IP following intracerebral inoculation with primary BSE isolate. We report genetic effects on IP that map to four chromosomal regions, and in addition we find significant factors of host environment, namely the age of the host's mother, the age of the host at infection, and an X-cytoplasm interaction in the host.

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Section: Discussionmentioning

confidence: 99%

Genetic and environmental factors modify bovine spongiform encephalopathy incubation period in mice

Manolakou

Beaton

McConnell

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

114

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“…These copper ions (up to four Cu + ) linked to M 3 and the most abundant was [M 3 + 3Cu + À 2H] + at m/z = 813.9 Th. The addition of 2Cu + is also possible on M 3ox at m/z = 750.0 Th but cannot be distinguished from the addition of 2Cu 2+ on M 3 . No addition of copper ions was obtained on the dimers, except when using a copper(II) salt where copper ions bound to the dimer M 3 + M 3ox were observed (see Scheme 3 and ESIw).…”

Section: Three-cysteine-containing Peptidementioning

confidence: 96%

The role of copper in cysteine oxidation: study of intra- and inter-molecular reactions in mass spectrometry

Prudent

Girault

2009

Metallomics

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Cysteine-containing peptide oxidation was studied both by using an inert platinum electrode and a sacrificial electrode (copper or zinc) generating metallic ions in electrospray ionization mass spectrometry (ESI-MS). Using peptides containing one, two and three cysteines, we have compared the different chemical and electrochemical oxidation pathways of cysteine (RS ÀII H) to cystine (RS ÀI S ÀI R) and to sulfenic, sulfinic and sulfonic acid (RS 0 OH, RS II O 2 H and RS IV O 3 H, respectively). In the absence of copper ions, intra-molecular reactions were the most abundant, whereas inter-molecular reactions were found to be enhanced by the presence of copper ions. These cations favor the formation of 2 : 1 (peptide : copper) complexes compared to 1 : 1 complexes, thus enhancing the formation of inter-molecular bridges. This study highlights the importance of the position of cysteine inside a peptide during disulfide bridge formation.

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“…This latter disease is caused by an inherited defect in copper excretion into the bile by the liver (16,17). The accumulation of copper results in liver and neurological disease (17,18). Excess Cu 2ϩ and Zn 2ϩ are also reported to be associated with neurodegenerative disorders such as Alzheimer's and Parkinson's diseases (18 -20).…”

Section: ؉mentioning

confidence: 99%

Copper and Zinc Inhibit Gαs Function

Gao¹,

Du²,

Patel

2005

Journal of Biological Chemistry

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؊ with the nucleotide-free G␣ s is sufficient to activate AC. Using antibodies to the N and C termini of G␣ s , we show that the Cu 2؉ interaction site on the G protein is in the C terminus. We conclude that Cu 2؉ and Zn 2؉ generate a nucleotide-free state of G␣ s and that, in the absence of any nucleotide, the ␥-phosphate mimic of GTP, AlF 4 ؊ , alters G␣ s structure sufficiently to permit stimulation of AC activity. Moreover, our finding that isoproterenolstimulated AC activity was more sensitive to inhibition by Cu 2؉ and Zn 2؉ as compared with forskolin-stimulated activity is consistent with G␣ s being a primary target of these cations in regulating the signaling from receptor to AC.

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The Role of Copper in Neurodegenerative Disease

Cited by 807 publications

References 92 publications

Genetic and environmental factors modify bovine spongiform encephalopathy incubation period in mice

Genetic and environmental factors modify bovine spongiform encephalopathy incubation period in mice

The role of copper in cysteine oxidation: study of intra- and inter-molecular reactions in mass spectrometry

Copper and Zinc Inhibit Gαs Function

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