ZCCHC17 is a master regulator of synaptic gene expression in Alzheimer's disease.

ABSTRACT: Motivation:In an effort to better understand the molecular drivers of synaptic and neurophysiologic dysfunction in Alzheimer's disease (AD), we analyzed neuronal gene expression data from human AD brain tissue to identify master regulators of synaptic gene expression. Results:Master regulator analysis identifies ZCCHC17 as normally supporting the expression of a network of synaptic genes, and predicts that ZCCHC17 dysfunction in AD leads to lower expression of these genes. We demonstrate that ZCCHC17 is normally expressed in neurons and is reduced early in the course of AD pathology. We show that ZCCHC17 loss in rat neurons leads to lower expression of the majority of the predicted synaptic targets and that ZCCHC17 drives the expression of a similar gene network in humans and rats. These f

SUBMITTER: Tomljanovic Z 

PROVIDER: S-EPMC5860362 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature