The Experts below are selected from a list of 1689 Experts worldwide ranked by ideXlab platform
John Collinge - One of the best experts on this subject based on the ideXlab platform.
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strain specific prion protein conformation determined by metal ions
Nature Cell Biology, 1999Co-Authors: Jonathan D F Wadsworth, Andrew F Hill, Susan Joiner, Graham S Jackson, Anthony R Clarke, John CollingeAbstract:In animals infected with a transmissible spongiform encephalopathy, or prion disease, conformational isomers (known as PrPSc Proteins) of the wild-type, host-encoded cellular prion protein (PrPc) accumulate. The infectious agents, prions, are composed mainly of these conformational isomers, with distinct prion isolates or strains being associated with different PrPSc conformations and patterns of glycosylation. Here we show that two different human PrPSc types, seen in clinically distinct subtypes of classical Creutzfeldt-Jakob disease, can be interconverted in vitro by altering their metal-ion occupancy. The dependence of PrPSc conformation on the binding of copper and zinc represents a new mechanism for post-translational modification of PrP and for the generation of multiple prion strains, with widespread implications for both the molecular classification and the pathogenesis of prion diseases in humans and animals.
Anthony R Clarke - One of the best experts on this subject based on the ideXlab platform.
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strain specific prion protein conformation determined by metal ions
Nature Cell Biology, 1999Co-Authors: Jonathan D F Wadsworth, Andrew F Hill, Susan Joiner, Graham S Jackson, Anthony R Clarke, John CollingeAbstract:In animals infected with a transmissible spongiform encephalopathy, or prion disease, conformational isomers (known as PrPSc Proteins) of the wild-type, host-encoded cellular prion protein (PrPc) accumulate. The infectious agents, prions, are composed mainly of these conformational isomers, with distinct prion isolates or strains being associated with different PrPSc conformations and patterns of glycosylation. Here we show that two different human PrPSc types, seen in clinically distinct subtypes of classical Creutzfeldt-Jakob disease, can be interconverted in vitro by altering their metal-ion occupancy. The dependence of PrPSc conformation on the binding of copper and zinc represents a new mechanism for post-translational modification of PrP and for the generation of multiple prion strains, with widespread implications for both the molecular classification and the pathogenesis of prion diseases in humans and animals.
Stanley B Prusiner - One of the best experts on this subject based on the ideXlab platform.
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β amyloid prions and the pathobiology of alzheimer s disease
Cold Spring Harbor Perspectives in Medicine, 2018Co-Authors: Joel C Watts, Stanley B PrusinerAbstract:Alzheimer's disease (AD) is the most common neurodegenerative disease in humans and will pose a considerable challenge to healthcare systems in the coming years. Aggregation of the β-amyloid (Aβ) peptide within the brain is thought to be an initiating event in AD pathogenesis. Many recent studies in transgenic mice have provided evidence that Aβ aggregates become self-propagating during disease, leading to a cascade of protein aggregation in the brain, which may underlie the progressive nature of AD. The ability to self-propagate and the existence of distinct "strains" reveals that Aβ aggregates exhibit many properties indistinguishable from those of prions composed of PrPSc Proteins. Here, we review the evidence that Aβ can become a prion during disease and discuss how Aβ prions may be important for understanding the pathobiology of AD.
Jonathan D F Wadsworth - One of the best experts on this subject based on the ideXlab platform.
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strain specific prion protein conformation determined by metal ions
Nature Cell Biology, 1999Co-Authors: Jonathan D F Wadsworth, Andrew F Hill, Susan Joiner, Graham S Jackson, Anthony R Clarke, John CollingeAbstract:In animals infected with a transmissible spongiform encephalopathy, or prion disease, conformational isomers (known as PrPSc Proteins) of the wild-type, host-encoded cellular prion protein (PrPc) accumulate. The infectious agents, prions, are composed mainly of these conformational isomers, with distinct prion isolates or strains being associated with different PrPSc conformations and patterns of glycosylation. Here we show that two different human PrPSc types, seen in clinically distinct subtypes of classical Creutzfeldt-Jakob disease, can be interconverted in vitro by altering their metal-ion occupancy. The dependence of PrPSc conformation on the binding of copper and zinc represents a new mechanism for post-translational modification of PrP and for the generation of multiple prion strains, with widespread implications for both the molecular classification and the pathogenesis of prion diseases in humans and animals.
Joel C Watts - One of the best experts on this subject based on the ideXlab platform.
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β amyloid prions and the pathobiology of alzheimer s disease
Cold Spring Harbor Perspectives in Medicine, 2018Co-Authors: Joel C Watts, Stanley B PrusinerAbstract:Alzheimer's disease (AD) is the most common neurodegenerative disease in humans and will pose a considerable challenge to healthcare systems in the coming years. Aggregation of the β-amyloid (Aβ) peptide within the brain is thought to be an initiating event in AD pathogenesis. Many recent studies in transgenic mice have provided evidence that Aβ aggregates become self-propagating during disease, leading to a cascade of protein aggregation in the brain, which may underlie the progressive nature of AD. The ability to self-propagate and the existence of distinct "strains" reveals that Aβ aggregates exhibit many properties indistinguishable from those of prions composed of PrPSc Proteins. Here, we review the evidence that Aβ can become a prion during disease and discuss how Aβ prions may be important for understanding the pathobiology of AD.
