The metabolism of copper and Wilson's disease

Cumings, J. N.

doi:10.1079/pns19620007

Cited by 17 publications

(11 citation statements)

References 19 publications

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“…Although histochemical studies have demonstrated that the substantia nigra contains large quantities of Fe3+, Cu2+, and Mn2+ (Warren et al, 1960;Cumings, 1968;Earle, 1968;Larsen et al, 1979;Dexter et al, 1989;Riederer et al, 1989;Uitti et al, 1989), other work has indicated that the first two metals at least are localized to storage granules within glial cells and are not endogenous to the neuromelanin granules in neurons (Barden, 197 1 ;Hill and Switzer, 1984;Hirsch et al, 1991). However, the very weak EPR signal from free radicals in unprocessed substantia nigra ( Fig.…”

Section: Paramagnetic Metal Ions In the Unprocessed Tissuesmentioning

confidence: 98%

Purified Human Neuromelanin, Synthetic Dopamine Melanin as a Potential Model Pigment, and the Normal Human Substantia Nigra: Characterization by Electron Paramagnetic Resonance Spectroscopy

Enochs

Nilges

Swartz

1993

Journal of Neurochemistry

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Neuromelanin is a poorly understood pigment that accumulates in catecholaminergic neurons during normal aging. Electron paramagnetic resonance spectroscopy, an especially effective technique for investigating melanins, is used in the present study to show unambiguously that neuromelanin is a melanin; however, it is not well modeled by synthetic dopamine melanin and thus is an atypical melanin. Some of the unusual features of neuromelanin can be explained by postulating two distinct sources for its free radicals, the dominant one possibly derived from a precursor containing sulfur. Examination of human substantia nigra by electron paramagnetic resonance spectroscopy during the purification of neuromelanin also demonstrates, contrary to some other studies, that a portion of the paramagnetic metal ions in this tissue are bound to the pigment in situ. Combined with previous histochemical data, these observations have implications for the mechanism through which neuromelanin accumulates in vivo and are consistent with its having a cytoprotective function under normal conditions, but a cytotoxic role at advanced ages and in patients with Parkinson's disease. Other results of this study show that homogenizing tissues during the purification of any natural pigment may cause contamination of the pigment by extraneous metal ions and that subsequent incubation in hot acid, though most effective in removing metal ions and hydrolyzing proteins, leads to degradation of melanin. A purification procedure using incubation in acid at room temperature, however, is well suited for identifying and characterizing unknown natural pigments by electron paramagnetic resonance spectroscopy.

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Section: Paramagnetic Metal Ions In the Unprocessed Tissuesmentioning

confidence: 98%

Purified Human Neuromelanin, Synthetic Dopamine Melanin as a Potential Model Pigment, and the Normal Human Substantia Nigra: Characterization by Electron Paramagnetic Resonance Spectroscopy

Enochs

Nilges

Swartz

1993

Journal of Neurochemistry

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“…Treatment with a chelating agent to increase the rate of elimination of copper may therefore produce clinical improvement similar to that observed by Cumings (1951Cumings ( , 1962 and by Walshe (1956) in cases of Wilson's disease.…”

Section: Cobaltmentioning

confidence: 55%

“…Two cases of secondary biliary cirrhosis had serum copper levels of 1.23 and 1.65 ttg./g. These raised serum copper levels in biliary cirrhosis are in marked contrast to the hypocupraemia seen in Wilson's disease (Cumings, 1962). …”

Section: Cobaltmentioning

confidence: 92%

Relation Between Cirrhosis and Trace Metal Content of Liver

Hunt¹,

Parr²,

Taylor³

et al. 1963

BMJ

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“…At best, only moderate improvement was reported in individual patients, and it was not comparable to the effect of copper chelation therapy seen in WD. In WD, despite cerebral copper concentrations are increased 5-10 fold [175][176][177], 3-12 months of chelating drug treatment lead to marked improvement of neurological symptoms in 70-80% patients [178]. Even in disorders with extensive diffuse cerebral iron deposits such as aceruloplasminemia, neuroferritinopathy, and SupSid, effects of chelation therapy occur at a much lower level.…”

Section: Discussionmentioning

confidence: 99%

Iron chelation in the treatment of neurodegenerative diseases

Dušek

Schneider

Aaseth

2016

Journal of Trace Elements in Medicine and Biology

106

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a b s t r a c tDisturbance of cerebral iron regulation is almost universal in neurodegenerative disorders. There is a growing body of evidence that increased iron deposits may contribute to degenerative changes. Thus, the effect of iron chelation therapy has been investigated in many neurological disorders including rare genetic syndromes with neurodegeneration with brain iron accumulation as well as common sporadic disorders such as Parkinson's disease, Alzheimer's disease, and multiple sclerosis. This review summarizes recent advances in understanding the role of iron in the etiology of neurodegeneration. Outcomes of studies investigating the effect of iron chelation therapy in neurodegenerative disorders are systematically presented in tables. Iron chelators, particularly the blood brain barrier-crossing compound deferiprone, are capable of decreasing cerebral iron in areas with abnormally high concentrations as documented by MRI. Yet, currently, there is no compelling evidence of the clinical effect of iron removal therapy on any neurological disorder. However, several studies indicate that it may prevent or slow down disease progression of several disorders such as aceruloplasminemia, pantothenate kinase-associated neurodegeneration or Parkinson's disease.

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The metabolism of copper and Wilson's disease

Cited by 17 publications

References 19 publications

Purified Human Neuromelanin, Synthetic Dopamine Melanin as a Potential Model Pigment, and the Normal Human Substantia Nigra: Characterization by Electron Paramagnetic Resonance Spectroscopy

Purified Human Neuromelanin, Synthetic Dopamine Melanin as a Potential Model Pigment, and the Normal Human Substantia Nigra: Characterization by Electron Paramagnetic Resonance Spectroscopy

Relation Between Cirrhosis and Trace Metal Content of Liver

Iron chelation in the treatment of neurodegenerative diseases

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