Suppression of eEF2 phosphorylation alleviates synaptic failure and cognitive deficits in mouse models of Down syndrome.

ABSTRACT:

Introduction

Cognitive impairment is a core feature of Down syndrome (DS), and the underlying neurobiological mechanisms remain unclear. Translation dysregulation is linked to multiple neurological disorders characterized by cognitive impairments. Phosphorylation of the translational factor eukaryotic elongation factor 2 (eEF2) by its kinase eEF2K results in inhibition of general protein synthesis.

Methods

We used genetic and pharmacological methods to suppress eEF2K in two lines of DS mouse models. We further applied multiple approaches to evaluate the effects of eEF2K inhibition on DS pathophysiology.

Results

We found that eEF2K signaling was overactive in the brain of patients with DS and DS mouse models. Inhibition of eEF2 phosphorylation through suppression of eE

SUBMITTER: Wang X 

PROVIDER: S-EPMC11350057 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature