Estrogen can not only regulates the NLRP3 and NF-κB signaling pathways through ERα and ERβ but also regulates inflammation levels, microglial polarization and astrocyte activity in the central nervous system through GPER-related signaling pathways to maintain immune homeostasis in the brain and rescue brain injury, hypomnesia and cognitive impairment [20, 21, 52, 54–56] (Fig. 3). Here, NFKB1 is linked to Cognitive impairment.