Group 1 mGluR stimulation rescues APOE4-mediated translation defects in neurons.

ABSTRACT: The E4 isoform of apolipoprotein (APOE4) is the most recognized risk factor for Alzheimer's disease, implicated in early neurodegeneration and impaired synaptic plasticity. In neurons, exposure to APOE4 disrupts basal and NMDAR-mediated calcium signaling, further disrupting protein synthesis response. Group 1 mGluRs, a major class of glutamate receptors, also play a critical role in synaptic plasticity through activity-dependent protein synthesis. In this study, we examine neuronal protein synthesis response to mGluR stimulation in the background of APOE4 treatment. In DIV15 primary cortical neurons from Sprague-Dawley rat embryos, exposure to APOE4 induces inhibition of protein synthesis, which is rescued by stimulation of mGluRs for 5 min. mGluR stimulation also rescued the APOE4-induced

SUBMITTER: Radhakrishna BK 

PROVIDER: S-EPMC12614780 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature