The Experts below are selected from a list of 27 Experts worldwide ranked by ideXlab platform
Mohamed Helal - One of the best experts on this subject based on the ideXlab platform.
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ALZHEIMER’S DISEASE: ANALYSIS OF A MATHEMATICAL MODEL INCORPORATING THE ROLE OF PRIONS
2016Co-Authors: Mohamed Helal, Erwan Hingant, Laurent Pujo-menjouet, F. WebbAbstract:ABSTRACT. We introduce a mathematical model of the in vivo progression of Alzheimer’s disease with focus on the role of prions in memory impairment. Our model consists of differential equations that de-scribe the dynamic formation of β-amyloid plaques based on the concentrations of Aβ oligomers, PrPC Proteins, and the Aβ-×-PrPC complex, which are hypothesized to be responsible for synaptic toxicity. We prove the well-posedness of the model and provided stability results for its unique equilibrium, when the polymerization rate of β-amyloid is constant and also when it is described by a power law. CONTENT
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Alzheimer's disease: analysis of a mathematical model incorporating the role of prions
Journal of Mathematical Biology, 2014Co-Authors: Mohamed Helal, Erwan Hingant, Laurent Pujo-menjouet, Glenn F. WebbAbstract:We introduce a mathematical model of the in vivo progression of Alzheimer's disease with focus on the role of prions in memory impairment. Our model consists of differential equations that describe the dynamic formation of {\beta}-amyloid plaques based on the concentrations of A{\beta} oligomers, PrPC Proteins, and the A{\beta}-x-PrPC complex, which are hypothesized to be responsible for synaptic toxicity. We prove the well-posedness of the model and provided stability results for its unique equilibrium, when the polymerization rate of {\beta}-amyloid is constant and also when it is described by a power law.
Scott Napper - One of the best experts on this subject based on the ideXlab platform.
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nanopore analysis reveals differences in structural stability of ovine PrPC Proteins corresponding to scrapie susceptible vrq and resistance arr genotypes
Prion, 2013Co-Authors: Claudia Avis Madampage, Kristen Marciniuk, Pekka Maattanen, Neil R Cashman, Andrew A Potter, Jeremy S Lee, Scott NapperAbstract:Species, as well as individuals within species, have unique susceptibilities to prion infection that are likely based on sequence differences in cellular prion protein (PrPC). Species barriers to transmission also reflect PrPC sequence differences. Defining the structure-activity relationship of PrPC/PrPSc with respect to infectivity/susceptibility will benefit disease understanding and assessment of transmission risks. Here, nanopore analysis is employed to investigate genotypes of sheep PrPC corresponding to differential susceptibilities to scrapie infection. Under non-denaturing conditions scrapie resistant (ARR) and susceptible (VRQ) genotypes display similar, type I (bumping) predominant event profiles, suggesting a conserved folding pattern. Under increasingly denaturing conditions both Proteins shift to type II (intercalation/translocation) events but with different sensitivities to unfolding. Specifically, when pre-incubated in 2M Gdn-HCl, the VRQ variant had more of type II events as compared with the ARR protein, suggesting a more flexible unfolding pattern. Addition of PrPSc-specific polyclonal antibody (YML) to the ARR variant, pre-incubated in 2M Gdn-HCl, reduced the number of type II events with no clear intercalation/translocation peak, whereas for VRQ, type II events above blockades of 90 pA bound YML. A second PrPSc-specific antibody (SN6b) to a different cryptic epitope reduced type II events for VRQ but not the ARR variant. Collectively, the event patterns associated with sequential denaturation, as well as interactions with PrPSc-specific antibodies, support unique patterns and/or propensities of misfolding between the genotypes. Overall, nanopore analysis identifies intermediate conformations that occur during the unfolding pathways of ARR and VRQ genotypes and may help to understand the correlation of structural properties that induce protein misfolding.
F. Webb - One of the best experts on this subject based on the ideXlab platform.
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ALZHEIMER’S DISEASE: ANALYSIS OF A MATHEMATICAL MODEL INCORPORATING THE ROLE OF PRIONS
2016Co-Authors: Mohamed Helal, Erwan Hingant, Laurent Pujo-menjouet, F. WebbAbstract:ABSTRACT. We introduce a mathematical model of the in vivo progression of Alzheimer’s disease with focus on the role of prions in memory impairment. Our model consists of differential equations that de-scribe the dynamic formation of β-amyloid plaques based on the concentrations of Aβ oligomers, PrPC Proteins, and the Aβ-×-PrPC complex, which are hypothesized to be responsible for synaptic toxicity. We prove the well-posedness of the model and provided stability results for its unique equilibrium, when the polymerization rate of β-amyloid is constant and also when it is described by a power law. CONTENT
Michael Marden - One of the best experts on this subject based on the ideXlab platform.
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Neuroglobin and Prion Cellular Localization: Investigation of a Potential Interaction
Journal of Molecular Biology, 2009Co-Authors: Christophe Lechauve, Human Rezaei, Chantal Celier, Laurent Kiger, Marisol Corral-debrinski, Sylvie Noinville, Cédric Chauvierre, Djemel Hamdane, Christine Pato, Michael MardenAbstract:Neuroglobin (Ngb) and the cellular prion protein (PrPC), Proteins of unknown function in the nervous system, are known to be expressed in the retina and have been observed in different rat retinal cells. The retina is the site of the highest concentration for Ngb, a heme protein of similar size and conformation to myoglobin. In this study, we demonstrated by immunohistochemical analysis of retinal colocalization of Ngb and PrPC in the ganglion cell layer. Considering for these two a common protective role in relation to oxidative stress and a possible transient contact during migration of PrPC through the eye or upon neuronal degradation, we undertook in vitro studies of the interaction of the purified Proteins. Mixing these two Proteins leads to rapid aggregation, even at submicromolar concentrations. As observed with the use of dynamic light scattering, particles comprising both Proteins evolve to hundreds of nanometers within several seconds, a first report showing that PrPC is able to form aggregates without major structural changes. The main effect would then appear to be a protein–protein interaction specific to the surface charge of the Ngb protein with PrPC Nterminal sequence. A dominant parameter is the solvent ionic force, which can significantly modify the final state of aggregation. PrPC, normally anchored to the cell membrane, is toxic in the cytoplasm, where Ngb is present; this could suggest an Ngb function of scavenging Proteins capable of forming deleterious aggregates considering a charge complementarity in the complex.
Erwan Hingant - One of the best experts on this subject based on the ideXlab platform.
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ALZHEIMER’S DISEASE: ANALYSIS OF A MATHEMATICAL MODEL INCORPORATING THE ROLE OF PRIONS
2016Co-Authors: Mohamed Helal, Erwan Hingant, Laurent Pujo-menjouet, F. WebbAbstract:ABSTRACT. We introduce a mathematical model of the in vivo progression of Alzheimer’s disease with focus on the role of prions in memory impairment. Our model consists of differential equations that de-scribe the dynamic formation of β-amyloid plaques based on the concentrations of Aβ oligomers, PrPC Proteins, and the Aβ-×-PrPC complex, which are hypothesized to be responsible for synaptic toxicity. We prove the well-posedness of the model and provided stability results for its unique equilibrium, when the polymerization rate of β-amyloid is constant and also when it is described by a power law. CONTENT
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Alzheimer's disease: analysis of a mathematical model incorporating the role of prions
Journal of Mathematical Biology, 2014Co-Authors: Mohamed Helal, Erwan Hingant, Laurent Pujo-menjouet, Glenn F. WebbAbstract:We introduce a mathematical model of the in vivo progression of Alzheimer's disease with focus on the role of prions in memory impairment. Our model consists of differential equations that describe the dynamic formation of {\beta}-amyloid plaques based on the concentrations of A{\beta} oligomers, PrPC Proteins, and the A{\beta}-x-PrPC complex, which are hypothesized to be responsible for synaptic toxicity. We prove the well-posedness of the model and provided stability results for its unique equilibrium, when the polymerization rate of {\beta}-amyloid is constant and also when it is described by a power law.
