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A mathematical model for the effects of amyloid beta on intracellular calcium

The accumulation of Alzheimer’s disease (AD) associated Amyloid beta (Aβ) oligomers can trigger aberrant intracellular calcium (Ca(2+)) levels by disrupting the intrinsic Ca(2+) regulatory mechanism within cells. These disruptions can cause changes in homeostasis levels that can have detrimental eff...

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Detalles Bibliográficos
Autores principales: Latulippe, Joe, Lotito, Derek, Murby, Donovan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6105003/
https://www.ncbi.nlm.nih.gov/pubmed/30133494
http://dx.doi.org/10.1371/journal.pone.0202503
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author Latulippe, Joe
Lotito, Derek
Murby, Donovan
author_facet Latulippe, Joe
Lotito, Derek
Murby, Donovan
author_sort Latulippe, Joe
collection PubMed
description The accumulation of Alzheimer’s disease (AD) associated Amyloid beta (Aβ) oligomers can trigger aberrant intracellular calcium (Ca(2+)) levels by disrupting the intrinsic Ca(2+) regulatory mechanism within cells. These disruptions can cause changes in homeostasis levels that can have detrimental effects on cell function and survival. Although studies have shown that Aβ can interfere with various Ca(2+) fluxes, the complexity of these interactions remains elusive. We have constructed a mathematical model that simulates Ca(2+) patterns under the influence of Aβ. Our simulations shows that Aβ can increase regions of mixed-mode oscillations leading to aberrant signals under various conditions. We investigate how Aβ affects individual flux contributions through inositol triphosphate (IP(3)) receptors, ryanodine receptors, and membrane pores. We demonstrate that controlling for the ryanodine receptor’s maximal kinetic reaction rate may provide a biophysical way of managing aberrant Ca(2+) signals. The influence of a dynamic model for IP(3) production is also investigated under various conditions as well as the impact of changes in membrane potential. Our model is one of the first to investigate the effects of Aβ on a variety of cellular mechanisms providing a base modeling scheme from which further studies can draw on to better understand Ca(2+) regulation in an AD environment.
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spelling pubmed-61050032018-09-15 A mathematical model for the effects of amyloid beta on intracellular calcium Latulippe, Joe Lotito, Derek Murby, Donovan PLoS One Research Article The accumulation of Alzheimer’s disease (AD) associated Amyloid beta (Aβ) oligomers can trigger aberrant intracellular calcium (Ca(2+)) levels by disrupting the intrinsic Ca(2+) regulatory mechanism within cells. These disruptions can cause changes in homeostasis levels that can have detrimental effects on cell function and survival. Although studies have shown that Aβ can interfere with various Ca(2+) fluxes, the complexity of these interactions remains elusive. We have constructed a mathematical model that simulates Ca(2+) patterns under the influence of Aβ. Our simulations shows that Aβ can increase regions of mixed-mode oscillations leading to aberrant signals under various conditions. We investigate how Aβ affects individual flux contributions through inositol triphosphate (IP(3)) receptors, ryanodine receptors, and membrane pores. We demonstrate that controlling for the ryanodine receptor’s maximal kinetic reaction rate may provide a biophysical way of managing aberrant Ca(2+) signals. The influence of a dynamic model for IP(3) production is also investigated under various conditions as well as the impact of changes in membrane potential. Our model is one of the first to investigate the effects of Aβ on a variety of cellular mechanisms providing a base modeling scheme from which further studies can draw on to better understand Ca(2+) regulation in an AD environment. Public Library of Science 2018-08-22 /pmc/articles/PMC6105003/ /pubmed/30133494 http://dx.doi.org/10.1371/journal.pone.0202503 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Latulippe, Joe
Lotito, Derek
Murby, Donovan
A mathematical model for the effects of amyloid beta on intracellular calcium
title A mathematical model for the effects of amyloid beta on intracellular calcium
title_full A mathematical model for the effects of amyloid beta on intracellular calcium
title_fullStr A mathematical model for the effects of amyloid beta on intracellular calcium
title_full_unstemmed A mathematical model for the effects of amyloid beta on intracellular calcium
title_short A mathematical model for the effects of amyloid beta on intracellular calcium
title_sort mathematical model for the effects of amyloid beta on intracellular calcium
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6105003/
https://www.ncbi.nlm.nih.gov/pubmed/30133494
http://dx.doi.org/10.1371/journal.pone.0202503
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