GluA2 palmitoylation by SELENOK modulates AMPAR assembly and synaptic plasticity in Alzheimer's disease.

ABSTRACT: Se is essential for central nervous system function, and its deficiency is strongly associated with cognitive decline, especially in neurodegenerative disorders such as Alzheimer's disease (AD). Although Se exerts its effects through selenoproteins, the molecular basis of its neuroprotective action remains unclear. Among selenoproteins, the endoplasmic reticulum (ER)-resident selenoprotein K (SELENOK) is closely linked to cognitive function and therapeutic potential in AD. Here, we examined how SELENOK regulates synaptic plasticity and contributes to Se-mediated neuroprotection in AD. Using age-gradient SELENOK knockout models and palmitoyl-proteomics, we identified GluA2 (formerly GluR2) as a key downstream target. Mechanistically, SELENOK enhanced the activity of DHHC6, an ER-localized p

SUBMITTER: Peng J 

PROVIDER: S-EPMC12446660 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature