4.6 Review

Mathematical Models of Death Signaling Networks

Journal

ENTROPY
Volume 24, Issue 10, Pages -

Publisher

MDPI
DOI: 10.3390/e24101402

Keywords

cell death; apoptosis; necroptosis; ferroptosis; pyroptosis; immunogenic cell death; regulatory networks; death execution pathways; mathematical models; computational analysis

Funding

  1. Breast Cancer Research Program [W81XWH-18-1-0722, BC171885]
  2. Public Health Service [NIH U01CA184902]

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This review provides an overview of the progress made by computational and systems biologists in characterizing different cell death regulatory mechanisms and emphasizes the importance and complexity of the cell death network. It also highlights the need for mathematical modeling and system-oriented approaches in understanding the dynamic behavior of this complex regulatory mechanism.
This review provides an overview of the progress made by computational and systems biologists in characterizing different cell death regulatory mechanisms that constitute the cell death network. We define the cell death network as a comprehensive decision-making mechanism that controls multiple death execution molecular circuits. This network involves multiple feedback and feed-forward loops and crosstalk among different cell death-regulating pathways. While substantial progress has been made in characterizing individual cell death execution pathways, the cell death decision network is poorly defined and understood. Certainly, understanding the dynamic behavior of such complex regulatory mechanisms can be only achieved by applying mathematical modeling and system-oriented approaches. Here, we provide an overview of mathematical models that have been developed to characterize different cell death mechanisms and intend to identify future research directions in this field.

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