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dc.contributor.authorPoshtkohi, Alireza
dc.contributor.authorWade, John
dc.contributor.authorMcDaid, Liam
dc.contributor.authorLiu, Junxiu
dc.contributor.authorL Dallas, Mark
dc.contributor.authorBithell, Angela
dc.date.accessioned2024-03-28T13:00:02Z
dc.date.available2024-03-28T13:00:02Z
dc.date.issued2024-03-21
dc.identifier.citationPoshtkohi , A , Wade , J , McDaid , L , Liu , J , L Dallas , M & Bithell , A 2024 , ' Mathematical Modeling of PI3K/Akt Pathway in Microglia ' , Neural Computation , vol. 36 , no. 4 , pp. 645–676 . https://doi.org/10.1162/neco_a_01643
dc.identifier.issn0899-7667
dc.identifier.otherORCID: /0000-0001-5636-1567/work/156578123
dc.identifier.urihttp://hdl.handle.net/2299/27678
dc.description© 2024 Massachusetts Institute of Technology. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1162/neco_a_01643
dc.description.abstractThe 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.en
dc.format.extent32
dc.format.extent2903809
dc.language.isoeng
dc.relation.ispartofNeural Computation
dc.titleMathematical Modeling of PI3K/Akt Pathway in Microgliaen
dc.contributor.institutionBiocomputation Research Group
dc.contributor.institutionDepartment of Computer Science
dc.contributor.institutionSchool of Physics, Engineering & Computer Science
dc.description.statusPeer reviewed
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85188802507&partnerID=8YFLogxK
rioxxterms.versionofrecord10.1162/neco_a_01643
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue


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