We have demonstrated that estradiol increased basal mitochondrial respiratory function and prevented the neurotoxic-induced decline in mitochondrial respiratory function [104]. This is consistent with the previous reports that estradiol is protective against cell death induced by energy depletion [149] and blocks the decrease in mitochondrial membrane potential induced by amyloid b in PC12 cells [93]. Thus estradiol may be able to prevent interruption of neuronal energy metabolism associated with neurodegeneration and may reduce APP expression and paired helical filament formation.