Neuronal calcineurin transcriptional targets parallel changes observed in Alzheimer disease brain.

ABSTRACT: Synaptic dysfunction and loss are core pathological features in Alzheimer disease (AD). In the vicinity of amyloid-β plaques in animal models, synaptic toxicity occurs and is associated with chronic activation of the phosphatase calcineurin (CN). Indeed, pharmacological inhibition of CN blocks amyloid-β synaptotoxicity. We therefore hypothesized that CN-mediated transcriptional changes may contribute to AD neuropathology and tested this by examining the impact of CN over-expression on neuronal gene expression in vivo. We found dramatic transcriptional down-regulation, especially of synaptic mRNAs, in neurons chronically exposed to CN activation. Importantly, the transcriptional profile parallels the changes in human AD tissue. Bioinformatics analyses suggest that both nuclear factor of act

SUBMITTER: Hopp SC 

PROVIDER: S-EPMC6181788 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature