These results underscore the functional relevance of XBP-1 in Aβ toxicity and degradation, and highlight the potentially pharmacodynamic value of dauricine in preventing the progression of AD.
These results reveal that both overlapping and disease-specific patterns of IRE1α-XBP1 and ATF6 target genes are activated in AD and ALS, which may be relevant to the development of new therapeutic strategies.
Analyses of expression levels in human AD brains showed that ADAM10 mRNA correlated with active XBP-1 (r=0.3120), but expression did not reach levels of healthy age-matched controls, suggesting deregulation of XBP-1 signaling.
The study supports a role for the -116C/G polymorphism of XBP1 gene in the pathogenesis of AD, and further studies with a larger sample size and detailed data should be performed in other populations.
Among target genes of XBP-1, expression of protein disulfide isomerase (PDI), but not glucose-regulated protein 78 (GRP78), was increased in AD, suggesting disturbed activation of the UPR in AD.