The convergence of these dysregulated upstream signals, encompassing energy sensing through AMPK, redox balance mediated by NOX4 and SIRT1, and developmental signaling via Wnt, upon a compromised Nrf2 node underscores the centrality of its failure in COPD pathogenesis [27,49,53,54]. This evidence concerns the gene NFE2L2 and chronic obstructive pulmonary disease.