Iron and copper in progressive demyelination – New lessons from Skogholt's disease

Aspli, Klaus T.; Flaten, Trond Peder; Roos, Per M.; Holmøy, Trygve; Skogholt, Jon H.; Aaseth, Jan

doi:10.1016/j.jtemb.2014.12.002

Cited by 23 publications

(13 citation statements)

References 63 publications

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“…Copper (Cu) as a part of the synthesis of myelin has a basic role in many neurodegenerative diseases ( 25 ). However, ceruloplasmin as a copper-transporting protein has high molecular weight, thus, it is unable to penetrate the blood brain barrier ( 26 ). So, in order to find the effect of copper in MS as a demyelinating process, the concentration of copper was measured in a different body fluid such as CSF and serum ( 23 , 27 – 30 ).…”

Section: Discussionmentioning

confidence: 99%

Comparison of serum Concentration of Se, Pb, Mg, Cu, Zn, between MS patients and healthy controls

Alizadeh¹,

Mehrpour²,

Nikkhah³

et al. 2016

Electron physician

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IntroductionMultiple Sclerosis (MS) is defined as one of the inflammatory autoimmune disorders and is common. Its exact etiology is unclear. There are some evidences on the role of environmental factors in susceptible genetics. The aim of this study is to evaluate the possible role of Selenium, Zinc, Copper, Lead and Magnesium metals in Multiple Sclerosis patients.MethodsIn the present analytical cross-sectional study, 56 individuals including 26 patients and 30 healthy controls were enrolled in the evaluation. The serum level of Se, Zn, Cu, Pb were quantified in graphite furnace conditions and flame conditions by utilizing an atomic absorption Perkin Elmer spectrophotometer 3030. The serum levels of Mg were measured by auto analyzer 1500 BT. The mean level of minerals (Zn, Pb, Cu, Mg, Se) in serum samples were compared in both cases and controls. The mean level of minerals (Zn, Pb, Cu, Mg, Se) in serum samples were compared in both cases and controls by using independent-samples t-test for normal distribution and Mann-Whitney U test as a non-parametric test. All statistical analyses were carried out using SPSS 11.0.ResultsAs well as the Zn, Cu, and Se, there was no significant difference between MS patients and healthy individuals in Pb concentrations (p-value = 0.11, 0.14, 0.32, 0.20 respectively) but the level of Mg was significantly different (p= 0.001).ConclusionAll serum concentrations of Zn, Pb, Se, Cu in both groups were in normal ranges and there was no difference in MS patients compared with the healthy group who were matched in genetics. Blood level of Mg was significantly lower in MS patients. But it should be noted that even with the low level of serum magnesium in MS patients, this value is still in the normal range.

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Section: Discussionmentioning

confidence: 99%

Comparison of serum Concentration of Se, Pb, Mg, Cu, Zn, between MS patients and healthy controls

Alizadeh¹,

Mehrpour²,

Nikkhah³

et al. 2016

Electron physician

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“…[ 46 ] The co-association of MS with Wilson's disease has been reported in a few cases [ 47 ]; moreover, high Cu levels in the cerebrospinal fluid (CSF) have been associated with the demyelinating process in both the central and peripheral nervous systems regarding Skogholt disease. [ 48 ] Additionally, one of the most relevant animal models of demyelination is obtained by the administration of cuprizone, [ 49 ] a Cu chelating mitochondrial toxin causing oligodendrocytes apoptosis and demyelination in the CNS. [ 50 ] Furthermore, the use of clioquinol, a Cu/Zn chelator, determined a reduction of the white matter damage in the spinal cord of an MS model in mice.…”

Section: Discussionmentioning

confidence: 99%

Is Geo-Environmental Exposure a Risk Factor for Multiple Sclerosis? A Population-Based Cross-Sectional Study in South-Western Sardinia

et al. 2016

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BackgroundSouth-Western Sardinia (SWS) is a high risk area for Multiple Sclerosis (MS) with high prevalence and spatial clustering; its population is genetically representative of Sardinians and presents a peculiar environment. We evaluated the MS environmental risk of specific heavy metals (HM) and geographical factors such as solar UV exposure and urbanization by undertaking a population-based cross-sectional study in SWS.MethodsGeochemical data on HM, UV exposure, urbanization and epidemiological MS data were available for all SWS municipalities. Principal Component Analysis (PCA) was applied to the geochemical data to reduce multicollinearity and confounding criticalities. Generalized Linear Mixed Models (GLMM) were applied to evaluate the causal effects of the potential risk factors, and a model selection was performed using Akaike Information Criterion.ResultsThe PCA revealed that copper (Cu) does not cluster, while two component scores were extracted: 'basic rocks', including cobalt, chromium and nickel, and 'ore deposits', including lead and zinc. The selected multivariable GLMM highlighted Cu and sex as MS risk factors, adjusting for age and 'ore deposits'. When the Cu concentration increases by 50 ppm, the MS odds are 2.827 (95% CI: 1.645; 5.07) times higher; females have a MS odds 2.04 times (95% CI: 1.59; 2.60) higher than males.ConclusionsThe high frequency of MS in industrialized countries, where pollution by HM and CO poisoning is widespread, suggests a relationship between environmental exposure to metals and MS. Hence, we suggested a role of Cu homeostasis in MS. This is a preliminary study aimed at generating hypotheses that will need to be confirmed further.

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“…It is known that chromate, which rapidly traverses biological membranes [34], exerts toxic effects on mitochondria [35,36]. Another cluster with PSP-resembling symptomatology has been described in a region that was previously active in iron and copper mining in eastern Norway [37]. This tauopathy was associated with the well-known mitochondrial toxicity of non-complexed iron [38].…”

Section: Progressive Supranuclear Palsymentioning

confidence: 99%

Xenobiotics, Trace Metals and Genetics in the Pathogenesis of Tauopathies

Aaseth

Buha

Wallace

et al. 2020

IJERPH

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Tauopathies are a disease group characterized by either pathological accumulation or release of fragments of hyperphosphorylated tau proteins originating from the central nervous system. The tau hypotheses of Parkinson’s and Alzheimer’s diseases contain a clinically diverse spectrum of tauopathies. Studies of case records of various tauopathies may reveal clinical phenotype characteristics of the disease. In addition, improved understanding of different tauopathies would disclose environmental factors, such as xenobiotics and trace metals, that can precipitate or modify the progression of the disorder. Important for diagnostics and monitoring of these disorders is a further development of adequate biomarkers, including refined neuroimaging, or proteomics. Our goal is to provide an in-depth review of the current literature regarding the pathophysiological roles of tau proteins and the pathogenic factors leading to various tauopathies, with the perspective of future advances in potential therapeutic strategies.

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Iron and copper in progressive demyelination – New lessons from Skogholt's disease

Cited by 23 publications

References 63 publications

Comparison of serum Concentration of Se, Pb, Mg, Cu, Zn, between MS patients and healthy controls

Comparison of serum Concentration of Se, Pb, Mg, Cu, Zn, between MS patients and healthy controls

Is Geo-Environmental Exposure a Risk Factor for Multiple Sclerosis? A Population-Based Cross-Sectional Study in South-Western Sardinia

Xenobiotics, Trace Metals and Genetics in the Pathogenesis of Tauopathies

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