Downregulation of Nrf2 deteriorates cognitive impairment in APP/PS1 mice by inhibiting mitochondrial biogenesis through the PPARγ/PGC1α signaling pathway

Nrf2 can directly regulate PGC1α transcription, and can also regulate PPARγ followed by binding to the PGC1α protein, thereby modulating mitochondrial biogenesis.Nrf2 downregulation reduces the expression of PPARγ and PGC1α proteins, thereby reducing their interaction. This suppression impairs mitochondrial biogenesis, exacerbates mitochondrial dysfunction, intensifies Aβ deposition and synaptic damage, and ultimately worsens cognitive impairment in AD mice.