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• W3121145612 startingPage "e0246116" @default.
• W3121145612 abstract "Alzheimer’s disease (AD) is a devastating illness affecting over 40 million people worldwide. Intraneuronal rise of amyloid beta in its oligomeric forms (iA β Os), has been linked to the pathogenesis of AD by disrupting cytosolic Ca 2+ homeostasis. However, the specific mechanisms of action are still under debate and intense effort is ongoing to improve our understanding of the crucial steps involved in the mechanisms of A β Os toxicity. We report the development of a mathematical model describing a proposed mechanism by which stimulation of Phospholipase C (PLC) by iA β O, triggers production of IP 3 with consequent abnormal release of Ca 2+ from the endoplasmic reticulum (ER) through activation of IP 3 receptor (IP 3 R) Ca 2+ channels. After validating the model using experimental data, we quantify the effects of intracellular rise in iA β Os on model solutions. Our model validates a dose-dependent influence of iA β Os on IP 3 -mediated Ca 2+ signaling. We investigate Ca 2+ signaling patterns for small and large iA β Os doses and study the role of various parameters on Ca 2+ signals. Uncertainty quantification and partial rank correlation coefficients are used to better understand how the model behaves under various parameter regimes. Our model predicts that iA β O alter IP 3 R sensitivity to IP 3 for large doses. Our analysis also shows that the upstream production of IP 3 can influence A β -driven solution patterns in a dose-dependent manner. Model results illustrate and confirm the detrimental impact of iA β Os on IP 3 signaling." @default.
• W3121145612 created "2021-02-01" @default.
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• W3121145612 date "2021-01-28" @default.
• W3121145612 modified "2023-09-26" @default.
• W3121145612 title "Quantifying the dose-dependent impact of intracellular amyloid beta in a mathematical model of calcium regulation in xenopus oocyte" @default.
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• W3121145612 doi "https://doi.org/10.1371/journal.pone.0246116" @default.
• W3121145612 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7842920" @default.
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• W3121145612 hasPublicationYear "2021" @default.
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