CDT2-controlled cell cycle reentry regulates the pathogenesis of Alzheimer's disease.

ABSTRACT:

Introduction

Altered cell cycle reentry has been observed in Alzheimer's disease (AD). Denticleless (DTL) was predicted as the top driver of a cell cycle subnetwork associated with AD.

Methods

We systematically investigated DTL expression in AD and studied the molecular, cellular, and behavioral endophenotypes triggered by DTL overexpression.

Results

We experimentally validated that CDT2, the protein encoded by DTL, activated cyclin-dependent kinases through downregulating P21, which induced tau hyperphosphorylation and Aβ toxicity, two hallmarks of AD. We demonstrated that cyclin-dependent kinases inhibition by roscovitine not only rescued CDT2-induced cognitive defects but also reversed expression changes induced by DTL overexpression. RNA-seq data from the DTL over

SUBMITTER: Huang F 

PROVIDER: S-EPMC6758558 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature