Figure 1.

Targeting host defense by up-regulating Nrf2 may inhibit pathological drivers of COPD. Activation of Nrf2 by small molecules increases genes that encode direct antioxidants (heme oxygenase 1 [Ho-1], superoxide dismutase1 [SOD1], catalase [cat], NADPH quinone reductase 1 [Nqo1]), GSH biosynthesizing enzymes (glutamate-cysteine ligase), electrophile detoxification enzymes (glutathione S-transferase, [Gsts]), catalytic and regulatory members of the proteasome system, and scavenger receptors (MARCO and CD36). This multifaceted cytoprotective response suppresses oxidative stress, endoplasmic reticulum (ER) stress, inflammation, immune dysregulation, and disruption of innate immune defenses induced by chronic cigarette smoke exposure.