Autophagy controls the hippocampal postsynaptic organization and affects cognition in a mouse model of Fragile X syndrome.

ABSTRACT: Dysregulated spine morphology is a common feature in the pathology of many neurodevelopmental and neuropsychiatric disorders. Overabundant immature dendritic spines in the hippocampus are causally related to cognitive deficits of Fragile X syndrome (FXS), the most common form of heritable intellectual disability. Recent findings from us and others indicate autophagy plays important roles in synaptic stability and morphology, and autophagy is downregulated in FXS neurons. However, the mechanism remains unclear. In this study, we identified that activated autophagy degrades the eukaryotic initiation factor 4G1 (eIF4G1) and postsynaptic density protein-95 (PSD-95) in hippocampal neurons of Fmr1 KO mice and FXS neurons from patients, which subsequently corrected the dysregulated postsynaptic o

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC12700825 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature