Fig. 3
The interaction between the Nrf2-KEAP1-ARE-NQO1, CREB-Nrf2/HO-1/NQO1, and NQO1-Nrf2-PI3K/Akt signaling pathways plays a crucial role in the regulation of oxidative stress. The interplay between these pathways leads to a coordinated cellular defense against oxidative stress. Following the occurrence of oxidative stress, nuclear factor erythroid 2-related factor 2 (Nrf2) is a key player in the transcriptional regulation of various genes involved in the antioxidant response, including NQO1. The CREB-Nrf2/HO-1/NQO1 pathway can synergistically enhance the expression of antioxidant enzymes when Nrf2 accumulates. Moreover, NQO1 has a bidirectional modulator effect with the PI3K/Akt signaling pathway to further enhancement of the anti-oxidative response. The modulation of the interaction between these pathways on cellular metabolism and their role in addressing oxidative stress could be a potential shared therapeutic target for the treatment of various neurological disorders. NQO1 can well connect various pathways and act as a bridge. It mainly protects nerve cells by resisting oxidative stress, enhancing cell metabolism, promoting cell survival, and preventing hypoxia. Interactions between these pathways may vary in different cell types and under different conditions [84, 97, 109,110,111,112]