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One explanation for this is attributed to the feedback regulation within the pathwaycontinuous NRF2 activation triggers the cellular program to express NRF2 transcriptional repressors (Figures 4A,B)

It receives input from the suprachiasmatic nucleus (SCN) of the hypothalamus, which acts as the body master clock, and translates that input into hormonal signals that synchronize virtually every biological process in your body

Nat Genet 2005

Preclinical evidence suggests that partial transporter inhibition may be sufficient to increase extracellular glycine levels and enhance NMDA receptor activation, whereas excessive inhibition could disturb the finely regulated balance of co-agonist availability and synaptic signaling (Javitt 2012