A delta-secretase-truncated APP fragment activates CEBPB, mediating Alzheimer's disease pathologies.

ABSTRACT: Amyloid-β precursor protein (APP) is sequentially cleaved by secretases and generates amyloid-β, the major components in senile plaques in Alzheimer's disease. APP is upregulated in human Alzheimer's disease brains. However, the molecular mechanism of how APP contributes to Alzheimer's disease pathogenesis remains incompletely understood. Here we show that truncated APP C586-695 fragment generated by δ-secretase directly binds to CCAAT/enhancer-binding protein beta (CEBPB), an inflammatory transcription factor, and enhances its transcriptional activity, escalating Alzheimer's disease-related gene expression and pathogenesis. The APP C586-695 fragment, but not full-length APP, strongly associates with CEBPB and elicits its nuclear translocation and augments the transcriptional activities on

SUBMITTER: Yao Y 

PROVIDER: S-EPMC8320270 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature