Execution gates in neurodegeneration: when neurons lose the ability to recover

This Perspective proposes the concept of “execution gates” in neurodegeneration: regulated commitment boundaries that may determine when stressed neurons transition from recoverable dysfunction to irreversible degeneration. The framework emphasizes neuronal recoverability as an experimentally measurable property and proposes delayed-rescue paradigms to define commitment boundaries. SARM1-mediated axon degeneration, integrated stress response/stress-granule biology, and TDP-43-associated dysfunction are considered as test cases. Preprint. This manuscript is currently under peer review at Molecular Neurodegeneration Advances.