Figure 2. Transcriptional regulation of Reductive Stress.

Cells in general, respond to oxidative stress by activating Nrf2, a master transcription factor that controls battery of antioxidant genes. Mutant R120G-CryAB protein mice displayed uncontrolled hyper-activation of Nrf2, with an over-amplification of Nrf2-dependent antioxidant genes. Though induction of Nrf2 has been shown to be promising in many acute models, the sustained and chronic amplification of Nrf2 pathway, however was not beneficial but for resulting in damaging hypertrophy. This forms the unique aspect of our model explaining that a protracted Nrf2 activation could over-compensate for the original stress due to lack of CryAB protein resulting in the observed “reductive stress”.