Round Scad-Derived Octapeptide WCPFSRSF Confers Neuroprotection by Regulating Akt/Nrf2/NFκB Signaling

We previously identified peptides derived from round scad as potential Nrf2 activators. However, the neuroprotection of these peptides is still unclear. In this study, we aimed to investigate the neuroprotective effect of WCPFSRSF against glutamate-induced neurotoxicity, and the memory-improving effects of WCPFSRSF in mice were also explored. Results showed that WCPFSRSF ameliorated oxidative stress by improving the activities of antioxidant enzymes and promoting the Nrf2-mediated endogenous defense system. Moreover, there is an interaction between the up-regulation of Nrf2 and the down-regulation of NFκB induced by the peptide, which was related to the generation of reactive oxygen species (ROS) and could be abolished by the Akt inhibitor LY294002. Further analysis demonstrated that WCPFSRSF may act as a radical scavenger and Nrf2 activator. The antioxidant and anti-inflammatory effects might be related to the Cys and Trp in WCPFSRSF. Moreover, WCPFSRSF could improve spatial memory impairment in sleep-deprived mice. Thus, this work provided evidence for WCPFSRSF as a potential candidate against neurotoxicity and memory deficits.