The Experts below are selected from a list of 234 Experts worldwide ranked by ideXlab platform
David R. Brown - One of the best experts on this subject based on the ideXlab platform.
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Metalloproteins and neuronal death
Metallomics : integrated biometal science, 2009Co-Authors: David R. BrownAbstract:Neurodegenerative diseases include Alzheimer’s and Parkinson’s disease that are very common and other diseases that are notorious but occur less often such as Creutzfeldt-Jakob disease. In each case a protein is closely linked to the pathology of these diseases. These proteins include alpha-synuclein, the prion protein and Aβ. Despite first being discovered because of aggregates of these amyloidogenic proteins found in the brains of patients, these proteins all exist in the healthy brain where their normal function involves binding of Metals. Recognition of these proteins as Metalloproteins implies that the diseases they are associated with are possibly diseases with altered Metal Metabolism at their heart. This review considers the evidence that cell death in these diseases involves not just the aggregated proteins but also the Metals they bind.
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The effects of prion protein expression on Metal Metabolism.
Molecular and cellular neurosciences, 2009Co-Authors: Silvia Kralovicova, Sarah N. Fontaine, Alexandra Alderton, Julia Alderman, K. Vala Ragnarsdottir, Steven J. Collins, David R. BrownAbstract:The prion protein is a glycoprotein that binds Metals such as copper and manganese. When converted to a proteinase resistant isoform it is associated with prion diseases such as Creutzfeldt-Jakob disease and bovine spongiform encephalopathy. Although, the co-ordination and Metal affinity of the prion protein has been well studied, the association of the protein with cellular Metal Metabolism has been less well investigated. We used transgenic manipulation of prion protein expression and other recombinant techniques to alter expression of known copper binding proteins to investigate the role of the prion protein in copper Metabolism. We found that changing the expression of the prion protein alters proteins associated with copper uptake, storage and export from the cell. In addition, alteration in the expression of superoxide dismutases increased prion protein expression dramatically. Reducing copper in the diet decreased expression of the prion protein in the brain while increased dietary manganese dramatically increased the protein's expression. Cellular prion infection also increased the expression of Metal transporting proteins and increased cellular manganese concentrations. Overall our results show a close link between cellular resistance to oxidative stress and also copper Metabolism. These findings are in line with previous data suggesting that the prion protein is an antioxidant and associated with copper uptake into cells. The disturbance to copper Metabolism, as a result of altered prion protein expression clearly demonstrates the important role of the prion protein in copper Metabolism. The implication is that prion protein expression has a homeostatic role in copper Metabolism.
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Copper and prion diseases.
Biochemical Society transactions, 2002Co-Authors: David R. BrownAbstract:Transmissible spongiform encephalopathies are diseases of animals and humans that are also termed prion diseases. These diseases are linked together because a normal brain glycoprotein termed the prion protein is converted to a readily detectable protease-resistant isoform. There is now strong evidence to suggest that apart from this difference in resistance a major difference between the isoforms is that the normal prion protein binds copper and has an anti-oxidant function. Brains from Creutzfeldt-Jakob disease patients and brains from mice with experimental mouse scrapie have been shown to have changes in the levels of both copper and manganese. There is growing evidence that links prion diseases to disturbances of Metal Metabolism.
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Metal toxicity and therapeutic intervention
Biochemical Society Transactions, 2002Co-Authors: David R. BrownAbstract:Transmissible spongiform encephalopathies are diseases of animals and humans that are also termed prion diseases. These diseases are linked together because a normal brain glycoprotein termed the prion protein is converted to a readily detectable protease-resistant isoform. There is now strong evidence to suggest that apart from this dierence in resistance a major dierence between the isoforms is that the normal prion protein binds copper and has an anti-oxidant function. Brains from Creutzfeldt‐Jakob disease patients and brains from mice with experimental mouse scrapie have been shown to have changes in the levels of both copper and manganese. There is growing evidence that links prion diseases to disturbances of Metal Metabolism.
Peter T. Clayton - One of the best experts on this subject based on the ideXlab platform.
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Inherited disorders of transition Metal Metabolism: an update
Journal of Inherited Metabolic Disease, 2017Co-Authors: Peter T. ClaytonAbstract:Elements with a biological role include six trace transition Metals: manganese, iron, cobalt, copper, zinc and molybdenum. Transition Metals participate in group transfer reactions such as glycosylation and phosphorylation and those that can transfer an electron by alternating between two redox states such as iron (3+/2+) and copper (2+/1+) are also very important in biological redox reactions including the reduction of molecular oxygen and the transport of oxygen. However, these trace Metals are also potentially toxic, generating reactive oxygen species through Fenton chemistry. Recently, a role of trace Metals in host defence (“nutritional immunity”) has been recognized. The host can deprive the pathogen of a trace Metal or poison it with a toxic concentration. Disorders leading to low concentrations of a trace Metal can often be treated by supplementing that Metal; disorders leading to excessively high concentrations can often be treated with chelating agents such as penicillamine and disodium calcium edetate. This update will address: i) the manganese/zinc transporters (because two new treatable disorders were described in 2016 – SLC39A8 deficiency and SLC39A14 deficiency); ii) copper transporter disorders because we need to improve the treatment of patients with neurological symptoms due to Wilson’s disease; and iii) iron homeostasis because recent progress in research into the Metabolism of iron and its regulation helps us better understand several inborn errors affecting these pathways.
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Inherited disorders of transition Metal Metabolism: an update
Journal of Inherited Metabolic Disease, 2017Co-Authors: Peter T. ClaytonAbstract:Elements with a biological role include six trace transition Metals: manganese, iron, cobalt, copper, zinc and molybdenum. Transition Metals participate in group transfer reactions such as glycosylation and phosphorylation and those that can transfer an electron by alternating between two redox states such as iron (3+/2+) and copper (2+/1+) are also very important in biological redox reactions including the reduction of molecular oxygen and the transport of oxygen. However, these trace Metals are also potentially toxic, generating reactive oxygen species through Fenton chemistry. Recently, a role of trace Metals in host defence (“nutritional immunity”) has been recognized. The host can deprive the pathogen of a trace Metal or poison it with a toxic concentration. Disorders leading to low concentrations of a trace Metal can often be treated by supplementing that Metal; disorders leading to excessively high concentrations can often be treated with chelating agents such as penicillamine and disodium calcium edetate. This update will address: i) the manganese/zinc transporters (because two new treatable disorders were described in 2016 – SLC39A8 deficiency and SLC39A14 deficiency); ii) copper transporter disorders because we need to improve the treatment of patients with neurological symptoms due to Wilson’s disease; and iii) iron homeostasis because recent progress in research into the Metabolism of iron and its regulation helps us better understand several inborn errors affecting these pathways.
Christelle Hureau - One of the best experts on this subject based on the ideXlab platform.
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a bioinorganic view of alzheimer s disease when misplaced Metal ions re direct the electrons to the wrong target
Chemistry: A European Journal, 2012Co-Authors: Peter Faller, Christelle HureauAbstract:Metal ions Cu, Zn and Fe, seem to play a pivotal role in Alzheimer’s disease and other neurodegenerative diseases. In order to understand this in a broader sense, one has to considerer the peculiarities of Metal Metabolism in the brain compared to most other tissues, as well as the importance of the redox active Metal ions, Fe and Cu, in oxygen Metabolism and the connected oxidative stress.
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A Bioinorganic View of Alzheimer’s Disease: When Misplaced Metal Ions (Re)direct the Electrons to the Wrong Target
Chemistry - A European Journal, 2012Co-Authors: Peter Faller, Christelle HureauAbstract:Metal ions Cu, Zn and Fe, seem to play a pivotal role in Alzheimer’s disease and other neurodegenerative diseases. In order to understand this in a broader sense, one has to considerer the peculiarities of Metal Metabolism in the brain compared to most other tissues, as well as the importance of the redox active Metal ions, Fe and Cu, in oxygen Metabolism and the connected oxidative stress.
Peter Faller - One of the best experts on this subject based on the ideXlab platform.
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a bioinorganic view of alzheimer s disease when misplaced Metal ions re direct the electrons to the wrong target
Chemistry: A European Journal, 2012Co-Authors: Peter Faller, Christelle HureauAbstract:Metal ions Cu, Zn and Fe, seem to play a pivotal role in Alzheimer’s disease and other neurodegenerative diseases. In order to understand this in a broader sense, one has to considerer the peculiarities of Metal Metabolism in the brain compared to most other tissues, as well as the importance of the redox active Metal ions, Fe and Cu, in oxygen Metabolism and the connected oxidative stress.
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A Bioinorganic View of Alzheimer’s Disease: When Misplaced Metal Ions (Re)direct the Electrons to the Wrong Target
Chemistry - A European Journal, 2012Co-Authors: Peter Faller, Christelle HureauAbstract:Metal ions Cu, Zn and Fe, seem to play a pivotal role in Alzheimer’s disease and other neurodegenerative diseases. In order to understand this in a broader sense, one has to considerer the peculiarities of Metal Metabolism in the brain compared to most other tissues, as well as the importance of the redox active Metal ions, Fe and Cu, in oxygen Metabolism and the connected oxidative stress.
Thomas Walczyk - One of the best experts on this subject based on the ideXlab platform.
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Environmental and Biomedical Applications of Natural Metal Stable Isotope Variations
Elements, 2009Co-Authors: Thomas D. Bullen, Thomas WalczykAbstract:Metal stable isotopes are now being used to trace Metal contaminants in the environment and as indicators of human systemic function where Metals play a role. Stable isotope abundance variations provide information about Metal sources and the processes affecting Metals in complex natural systems, complementing information gained from surrogate tracers, such as Metal abundance ratios or biochemical markers of Metal Metabolism. The science is still in its infancy, but the results of initial studies confirm that Metal stable isotopes can provide a powerful tool for forensic and biomedical investigations.