Mathematical model for NF-kappaB-driven proliferation of adult neural stem cells.

Abstract:

:Neural stem cells (NSCs) are early precursors of neuronal and glial cells. NSCs are capable of generating identical progeny through virtually unlimited numbers of cell divisions (cell proliferation), producing daughter cells committed to differentiation. Nuclear factor kappa B (NF-kappaB) is an inducible, ubiquitous transcription factor also expressed in neurones, glia and neural stem cells. Recently, several pieces of evidence have been provided for a central role of NF-kappaB in NSC proliferation control. Here, we propose a novel mathematical model for NF-kappaB-driven proliferation of NSCs. We have been able to reconstruct the molecular pathway of activation and inactivation of NF-kappaB and its influence on cell proliferation by a system of nonlinear ordinary differential equations. Then we use a combination of analytical and numerical techniques to study the model dynamics. The results obtained are illustrated by computer simulations and are, in general, in accordance with biological findings reported by several independent laboratories. The model is able to both explain and predict experimental data. Understanding of proliferation mechanisms in NSCs may provide a novel outlook in both potential use in therapeutic approaches, and basic research as well.

journal_name

Cell Prolif

journal_title

Cell proliferation

authors

Piotrowska MJ,Widera D,Kaltschmidt B,an der Heiden U,Kaltschmidt C

doi

10.1111/j.1365-2184.2006.00403.x

subject

Has Abstract

pub_date

2006-12-01 00:00:00

pages

441-55

issue

6

eissn

0960-7722

issn

1365-2184

pii

CPR403

journal_volume

39

pub_type

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