Dietary supplementation with tBHQ, an Nrf2 stabilizer molecule, confers neuroprotection against apoptosis in amyloid beta-injected rat.

摘要

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 beta (Abeta) can be attenuated by tBHQ, an Nrf2 stabilizer, Using an Abeta injection model. We demonstrated that pre-activation of endogenous Nrf2 by tBHQ attenuated Abeta-induced caspase-3 expression. tBHQ enhanced GSH, decreased MDA level, and inhibited NF-kappaB. This investigation provides the first documentation of tBHQ's neuroprotective effect through decrease of Abeta 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 Abeta injection protected against the oxidative damage, apoptosis and Abeta accumulation in rats.