Deletion of SH2D5 alleviates epileptic seizures and NMDAR expression via autophagic degradation of STAT1.

ABSTRACT: Epilepsy is a common neurological disorder resulting from an imbalance between neuronal excitation and inhibition. Synapses play a pivotal role in the pathogenesis of epilepsy. Src-homology 2 (SH2) domain-containing protein 5 (SH2D5) is highly expressed in the brain and is implicated in the regulation of synaptic function. However, its role and mechanism in epilepsy remain unclear. In this study, we found that SH2D5 was predominantly localized to pyramidal neurons in the mouse hippocampus and was upregulated in the hippocampus of epileptic brains. KO of Sh2d5 in the hippocampus alleviated both the susceptibility to and severity of epileptic activity. Mechanistically, SH2D5 regulated N-methyl-D-aspartate receptor-mediated (NMDAR-mediated) excitatory synaptic transmission by altering the pro

SUBMITTER: Guo H 

PROVIDER: S-EPMC12406720 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature