Nuclear factor erythroid 2-related factor 2 (Nrf2) coordinates the up-regulation of cytoprotective genes via the antioxidant response element (ARE). There is significant evidence that oxidative stress is a critical event in the pathogenesis of AD. Considering the protective role of Nrf2 against oxidative injury, we studied to determine whether in vivo toxicity of amyloid â (Aâ) can be attenuated by tBHQ, an Nrf2 stabilizer, Using an Aâ injection model. We demonstrated that pre-activation of endogenous Nrf2 by tBHQ attenuated Aâ-induced caspase-3 expression. tBHQ enhanced GSH, decreased MDA level, and inhibited NF-êB. This investigation provides the first documentation of tBHQ's neuroprotective effect through decrease of Aâ accumulation in rat brain. Our results show the involvement of Hsp-70 in this protective effect. In summary tBHQ treatment for 1 week prior to Aâ injection protected against the oxidative damage, apoptosis and Aâ accumulation in rats.
Amyloid beta-Peptides Animals