摘要：SummaryGlia, 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.Graphical AbstractDisplay OmittedHighlights•We present a computational model for disease onset of neurodegeneration•Healthy neuron-glia crosstalk balances seed removal and resolution of inflammation•Warning signs prior to onset are slowed reactivity and increased collateral damage•Analogous processes are found in Alzheimer disease and multiple sclerosisBioinformatics; Mathematical Biosciences; Neuroscience; Systems Biology; Systems Neuroscience
