IRF1 ameliorates synaptic dysfunction through the modulation of O-GlcNAcylation on GluN1 subunit of NMDAR.

ABSTRACT:

Background

Synaptic dysfunction, which occurs before the formation of amyloid plaques (Aβ) and neurofibrillary tangles (NFTs), is strongly associated with cognitive deficits and represents major early clinical features of Alzheimer's disease (AD). Abnormal NMDAR signaling emerges as a noticeable feature of synaptic dysfunctions in AD. Nonetheless, the underlying mechanisms of NMDAR dysfunctions remain unclear.

Methods

3xTg-AD mice were injected with AAV-IRF1. Cognitive function was assessed using behavioral tests, while biochemical and immunofluorescence analyses were conducted to evaluate the protein levels of IRF-1, OGA, subunits of NMDAR, O-GlcNAcylation of NMDAR subunits, and internalization of NMDA receptors. Synaptic alterations in the hippocampus were detected by elec

SUBMITTER: Fan X 

PROVIDER: S-EPMC12482151 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature