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NRF2–KEAP1 as a Redox Signal-Resolution Circuit: Beyond the Antioxidant Switch
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DOI：10.1016/j.pbiomolbio.2026.03.005.png)
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Abstract
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• The Nrf2-Keap1 pathway operates as a redox signal-resolution circuit, not a binary switch. • Signal duration and resolution, rather than peak activation, determine biological outcomes. • Keap1, ubiquitination, autophagy, and metabolism form an active termination module. • Pathology arises from distinct circuit failure modes, not excessive Nrf2 activation. • Therapeutic focus should shift from activation to restoring signaling dynamics.
Keywords:
Nrf2-Keap1 pathway
redox signaling
signal resolution
ubiquitination
autophagy
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