ABSTRACT
We initially investigated the involvement of familial AD-linked PS1 mutants in the UPR. Our data showed that a PS1 mutant altered UPR signaling and indicated that this alteration may contribute to the pathogenic mechanism in the brains of familial AD patients. According to the so-called amyloid hypothesis, Aβ accumulation is the pivotal event in sporadic AD cases as well as in familial AD. Therefore, we studied the relationship between Aβ accumulation and the UPR. We found that, in neurons exposed to Aβ, the UPR was stimulated to activate ER-resident caspases. We also found that, in the neurons whose UPR was disturbed, Aβ production was elevated. This brief review focuses on our work examining the pathology of AD and ER stress interaction.
