How Repair-or-Dispose Decisions Under Stress Can Initiate Disease Progression

Andreas Nold; Danylo Batulin; Katharina Birkner; Stefan Bittner; Tatjana Tchumatchenko

doi:10.1016/j.isci.2020.101701

How Repair-or-Dispose Decisions Under Stress Can Initiate Disease Progression

iScience. 2020 Oct 22;23(11):101701. doi: 10.1016/j.isci.2020.101701. eCollection 2020 Nov 20.

Authors

Andreas Nold¹, Danylo Batulin^{1

2}, Katharina Birkner³, Stefan Bittner³, Tatjana Tchumatchenko¹

Affiliations

¹ Theory of Neural Dynamics, Max Planck Institute for Brain Research, 60438 Frankfurt am Main, Germany.
² Frankfurt Institute for Advanced Studies (FIAS), 60438 Frankfurt am Main, Germany.
³ Department of Neurology, Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany.

Abstract

Glia, the helper cells of the brain, are essential in maintaining neural resilience across time and varying challenges: By reacting to changes in neuronal health glia carefully balance repair or disposal of injured neurons. Malfunction of these interactions is implicated in many neurodegenerative diseases. We present a reductionist model that mimics repair-or-dispose decisions to generate a hypothesis for the cause of disease onset. The model assumes four tissue states: healthy and challenged tissue, primed tissue at risk of acute damage propagation, and chronic neurodegeneration. We discuss analogies to progression stages observed in the most common neurodegenerative conditions and to experimental observations of cellular signaling pathways of glia-neuron crosstalk. The model suggests that the onset of neurodegeneration can result as a compromise between two conflicting goals: short-term resilience to stressors versus long-term prevention of tissue damage.

Keywords: Bioinformatics; Mathematical Biosciences; Neuroscience; Systems Biology; Systems Neuroscience.