Geographic Accumulation of Creutzfeldt-Jakob Disease in Slovakia - Environmental Metal Imbalance as a Possible Cofactor

Slivarichova, Dana; Mitrová, E; Ursı́nyová, Monika; Uhnáková, Iveta; Koščová, Silvia; Wsólová, Ladislava

doi:10.21101/cejph.a3667

Cited by 21 publications

(14 citation statements)

References 33 publications

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“…Assuming that humans would behave like mice, it remains to determine which life events have increased oxidative insults in offspring that did not in their parents. Moreover, a recent study in the E200K CJD cluster of Slovakia reported an unbalance of manganese/copper concentration in brain tissues of genetic CJD cases in comparison to controls suggesting that metal disequilibrium might act as exogenous co-factor for the development of disease [32], but great caution is needed in the interpretation of these data.…”

Section: Discussionmentioning

confidence: 99%

Age at Death of Creutzfeldt-Jakob Disease in Subsequent Family Generation Carrying the E200K Mutation of the Prion Protein Gene

et al. 2013

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BackgroundThe E200K mutation of the prion protein gene (PRNP) is the most frequent amino acid substitution in genetic Creutzfeldt-Jakob disease and is the only one responsible for the appearance of clustered cases in the world. In the Israel and Slovakian clusters, age of disease onset was reduced in successive generations but the absence of a clear molecular basis raised the possibility that this event was an observational bias. The aim of the present study was to investigate possible selection biases or confounding factors related to anticipation in E200K CJD patients belonging to a cluster in Southern Italy.MethodsClinical and demographical data of 41 parent-offspring pairs from 19 pedigrees of the Italian cluster of E200K patients were collected. Age at death of parents was compared with age at death of E200K CJD offspring. Subgroup analyses were performed for controlling possible selection biases, confounding factors, or both.ResultsThe mean age at death/last follow-up of the parent generation was 71.4 years while that of CJD offspring was 59.3 years with an estimated anticipation of 12.1 years. When the same analysis was performed including only parents with CJD or carrying the E200K mutation (n = 26), the difference between offspring and parents increased to 14.8 years.ConclusionsThese results show that early age at death occurs in offspring of families carrying the E200K PRNP mutation and that this event is not linked to observational biases. Although molecular or environmental bases for this occurrence remain unsettled, this information is important for improving the accuracy of information to give to mutated carriers.

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Section: Discussionmentioning

confidence: 99%

Age at Death of Creutzfeldt-Jakob Disease in Subsequent Family Generation Carrying the E200K Mutation of the Prion Protein Gene

et al. 2013

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“…Copper deficiency can cause many types of abnormalities, including anemia, skeletal defects, degeneration of the nervous system, reproductive failure, pronounced cardiovascular lesions, elevated blood cholesterol, impaired immunity, and defects in the pigmentation and structure of hair. Copper is also important for the prevention or moderation of certain neurodegenerative disease, including Parkinson's, Wilson's, Menkes, Alzheimer's, and prion diseases …”

Section: Copper and Neurodegenerative Disordersmentioning

confidence: 99%

“…Copper is also important for the prevention or moderation of certain neurodegenerative disease, including Parkinson's, Wilson's, Menkes, Alzheimer's, [73] and prion diseases. [74][75][76][77][78][79][80][81][82] In many copper-binding enzymes, the biological role of copper involves changing its oxidation state through the following oxidation-reduction reactions:…”

Section: Copper and Neurodegenerative Disordersmentioning

confidence: 99%

Utilizing NMR and EPR spectroscopy to probe the role of copper in prion diseases

Emwas

Al‐Talla

Guo

et al. 2013

Magnetic Reson in Chemistry

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Copper is an essential nutrient for the normal development of the brain and nervous system, although the hallmark of several neurological diseases is a change in copper concentrations in the brain and central nervous system. Prion protein (PrP) is a copper-binding, cell-surface glycoprotein that exists in two alternatively folded conformations: a normal isoform (PrP(C)) and a disease-associated isoform (PrP(Sc)). Prion diseases are a group of lethal neurodegenerative disorders that develop as a result of conformational conversion of PrP(C) into PrP(Sc). The pathogenic mechanism that triggers this conformational transformation with the subsequent development of prion diseases remains unclear. It has, however, been shown repeatedly that copper plays a significant functional role in the conformational conversion of prion proteins. In this review, we focus on current research that seeks to clarify the conformational changes associated with prion diseases and the role of copper in this mechanism, with emphasis on the latest applications of NMR and EPR spectroscopy to probe the interactions of copper with prion proteins.

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“…High Mn 2+ levels and increased Mn 2+ /Cu 2+ ratios were observed in these CJD brains (Slivarichová et al, 2011). The link between Mn 2+ and prion infection was also evidenced at the cellular level (Pass et al, 2015).…”

Section: Prion Protein Binds Transition Metalsmentioning

confidence: 95%

Metal Dyshomeostasis and Their Pathological Role in Prion and Prion-Like Diseases: The Basis for a Nutritional Approach

Toni¹,

Massimino

Mario

et al. 2017

Front. Neurosci.

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Metal ions are key elements in organisms' life acting like cofactors of many enzymes but they can also be potentially dangerous for the cell participating in redox reactions that lead to the formation of reactive oxygen species (ROS). Any factor inducing or limiting a metal dyshomeostasis, ROS production and cell injury may contribute to the onset of neurodegenerative diseases or play a neuroprotective action. Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, are a group of fatal neurodegenerative disorders affecting the central nervous system (CNS) of human and other mammalian species. The causative agent of TSEs is believed to be the scrapie prion protein PrPSc, the β sheet-rich pathogenic isoform produced by the conformational conversion of the α-helix-rich physiological isoform PrPC. The peculiarity of PrPSc is its ability to self-propagate in exponential fashion in cells and its tendency to precipitate in insoluble and protease-resistance amyloid aggregates leading to neuronal cell death. The expression “prion-like diseases” refers to a group of neurodegenerative diseases that share some neuropathological features with prion diseases such as the involvement of proteins (α-synuclein, amyloid β, and tau) able to precipitate producing amyloid deposits following conformational change. High social impact diseases such as Alzheimer's and Parkinson's belong to prion-like diseases. Accumulating evidence suggests that the exposure to environmental metals is a risk factor for the development of prion and prion-like diseases and that metal ions can directly bind to prion and prion-like proteins affecting the amount of amyloid aggregates. The diet, source of metal ions but also of natural antioxidant and chelating agents such as polyphenols, is an aspect to take into account in addressing the issue of neurodegeneration. Epidemiological data suggest that the Mediterranean diet, based on the abundant consumption of fresh vegetables and on low intake of meat, could play a preventive or delaying role in prion and prion-like neurodegenerative diseases. In this review, metal role in the onset of prion and prion-like diseases is dealt with from a nutritional, cellular, and molecular point of view.

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Geographic Accumulation of Creutzfeldt-Jakob Disease in Slovakia - Environmental Metal Imbalance as a Possible Cofactor

Cited by 21 publications

References 33 publications

Age at Death of Creutzfeldt-Jakob Disease in Subsequent Family Generation Carrying the E200K Mutation of the Prion Protein Gene

Age at Death of Creutzfeldt-Jakob Disease in Subsequent Family Generation Carrying the E200K Mutation of the Prion Protein Gene

Utilizing NMR and EPR spectroscopy to probe the role of copper in prion diseases

Metal Dyshomeostasis and Their Pathological Role in Prion and Prion-Like Diseases: The Basis for a Nutritional Approach

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