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. 2020 May 1;10(5):702. doi: 10.3390/biom10050702

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© 2020 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Representative model of the NRF2 signaling pathway activation in myotonic dystrophy 1 (DM1), based on literature evidences. Brain-derived neurotrophic factor (BDNF) activation of PI3K/AKT pathway determines the inhibitory phosphorylation of GSK3β by blocking NRF2/KEAP-1-indipendent degradation. As BDNF is a NRF2 target, this can start a positive feedback contributing to NRF2 activation. At the same time, the transcription of NRF2 antioxidant target genes reduces oxidative stress in DM1 cells and the pro-inflammatory cytokine IL-1β levels.