D2HGDH Deficiency Regulates Seizures through GSH/Prdx6/ROS-Mediated Excitatory Synaptic Activity.

ABSTRACT: Current antiepileptic drugs are ineffective in one-third of patients with epilepsy; however, identification of genes involved in epilepsy can enable a precision medicine approach. Here, it is demonstrated that downregulating D-2-hydroxyglutarate dehydrogenase (D2HGDH) enhances susceptibility to epilepsy. Furthermore, its potential involvement in the seizure network through synaptic function modulation is investigated. D2HGDH knockdown reduces the glutathione reduced (GSH)/glutathione oxidized (GSSG) ratio and elevates reactive oxygen species (ROS) levels within neurons. Oxidative stress may play a crucial role in the pathogenesis of epilepsy. The specific contribution of each pathway varies among patients, highlighting the complexity of this disease. In this study, downregulation of D2HGDH

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC11967838 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature