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Mathematical Modeling of PI3K/Akt Pathway in Microglia.

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Title: Mathematical Modeling of PI3K/Akt Pathway in Microglia.
Authors: Poshtkohi, Alireza (AUTHOR), Wade, John (AUTHOR), McDaid, Liam (AUTHOR), Liu, Junxiu (AUTHOR), Dallas, Mark L. (AUTHOR), Bithell, Angela (AUTHOR)
Source: Neural Computation. Apr2024, Vol. 36 Issue 4, p645-676. 32p.
Subjects: PI3K/AKT pathway, Calcium ions, Microglia, Mathematical models, Mathematical optimization, Purinergic receptors, Phosphoinositides
Abstract: The motility of microglia involves intracellular signaling pathways that are predominantly controlled by changes in cytosolic Ca 2+ and activation of PI3K/Akt (phosphoinositide-3-kinase/protein kinase B). In this letter, we develop a novel biophysical model for cytosolic Ca 2+ activation of the PI3K/Akt pathway in microglia where Ca 2+ influx is mediated by both P2Y purinergic receptors (P2YR) and P2X purinergic receptors (P2XR). The model parameters are estimated by employing optimization techniques to fit the model to phosphorylated Akt (pAkt) experimental modeling/in vitro data. The integrated model supports the hypothesis that Ca 2+ influx via P2YR and P2XR can explain the experimentally reported biphasic transient responses in measuring pAkt levels. Our predictions reveal new quantitative insights into P2Rs on how they regulate Ca 2+ and Akt in terms of physiological interactions and transient responses. It is shown that the upregulation of P2X receptors through a repetitive application of agonist results in a continual increase in the baseline [Ca 2+ ], which causes the biphasic response to become a monophasic response which prolongs elevated levels of pAkt. [ABSTRACT FROM AUTHOR]
Copyright of Neural Computation is the property of MIT Press and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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DbLabel: Psychology and Behavioral Sciences Collection
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PubTypeId: academicJournal
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  Data: Mathematical Modeling of PI3K/Akt Pathway in Microglia.
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  Data: <searchLink fieldCode="AR" term="%22Poshtkohi%2C+Alireza%22">Poshtkohi, Alireza</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wade%2C+John%22">Wade, John</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22McDaid%2C+Liam%22">McDaid, Liam</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Liu%2C+Junxiu%22">Liu, Junxiu</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Dallas%2C+Mark+L%2E%22">Dallas, Mark L.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bithell%2C+Angela%22">Bithell, Angela</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22Neural+Computation%22">Neural Computation</searchLink>. Apr2024, Vol. 36 Issue 4, p645-676. 32p.
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  Data: <searchLink fieldCode="DE" term="%22PI3K%2FAKT+pathway%22">PI3K/AKT pathway</searchLink><br /><searchLink fieldCode="DE" term="%22Calcium+ions%22">Calcium ions</searchLink><br /><searchLink fieldCode="DE" term="%22Microglia%22">Microglia</searchLink><br /><searchLink fieldCode="DE" term="%22Mathematical+models%22">Mathematical models</searchLink><br /><searchLink fieldCode="DE" term="%22Mathematical+optimization%22">Mathematical optimization</searchLink><br /><searchLink fieldCode="DE" term="%22Purinergic+receptors%22">Purinergic receptors</searchLink><br /><searchLink fieldCode="DE" term="%22Phosphoinositides%22">Phosphoinositides</searchLink>
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  Label: Abstract
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  Data: The motility of microglia involves intracellular signaling pathways that are predominantly controlled by changes in cytosolic Ca 2+ and activation of PI3K/Akt (phosphoinositide-3-kinase/protein kinase B). In this letter, we develop a novel biophysical model for cytosolic Ca 2+ activation of the PI3K/Akt pathway in microglia where Ca 2+ influx is mediated by both P2Y purinergic receptors (P2YR) and P2X purinergic receptors (P2XR). The model parameters are estimated by employing optimization techniques to fit the model to phosphorylated Akt (pAkt) experimental modeling/in vitro data. The integrated model supports the hypothesis that Ca 2+ influx via P2YR and P2XR can explain the experimentally reported biphasic transient responses in measuring pAkt levels. Our predictions reveal new quantitative insights into P2Rs on how they regulate Ca 2+ and Akt in terms of physiological interactions and transient responses. It is shown that the upregulation of P2X receptors through a repetitive application of agonist results in a continual increase in the baseline [Ca 2+ ], which causes the biphasic response to become a monophasic response which prolongs elevated levels of pAkt. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
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  Data: <i>Copyright of Neural Computation is the property of MIT Press and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
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    Identifiers:
      – Type: doi
        Value: 10.1162/neco_a_01643
    Languages:
      – Code: eng
        Text: English
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      Pagination:
        PageCount: 32
        StartPage: 645
    Subjects:
      – SubjectFull: PI3K/AKT pathway
        Type: general
      – SubjectFull: Calcium ions
        Type: general
      – SubjectFull: Microglia
        Type: general
      – SubjectFull: Mathematical models
        Type: general
      – SubjectFull: Mathematical optimization
        Type: general
      – SubjectFull: Purinergic receptors
        Type: general
      – SubjectFull: Phosphoinositides
        Type: general
    Titles:
      – TitleFull: Mathematical Modeling of PI3K/Akt Pathway in Microglia.
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          Name:
            NameFull: Poshtkohi, Alireza
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            NameFull: Wade, John
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            NameFull: McDaid, Liam
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            NameFull: Liu, Junxiu
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            – D: 01
              M: 04
              Text: Apr2024
              Type: published
              Y: 2024
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              Value: 36
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