Pharmacological induction of AMFR increases functional EAAT2 oligomer levels and reduces epileptic seizures in mice.

ABSTRACT: Dysregulation of excitatory amino acid transporter 2 (EAAT2) contributes to the development of temporal lobe epilepsy (TLE). Several strategies for increasing total EAAT2 levels have been proposed. However, the mechanism underlying the oligomeric assembly of EAAT2, impairment of which inhibits the formation of functional oligomers by EAAT2 monomers, is still poorly understood. In the present study, we identified E3 ubiquitin ligase AMFR as an EAAT2-interacting protein. AMFR specifically increased the level of EAAT2 oligomers rather than inducing protein degradation through K542-specific ubiquitination. By using tissues from humans with TLE and epilepsy model mice, we observed that AMFR and EAAT2 oligomer levels were simultaneously decreased in the hippocampus. Screening of 2386 FDA-approve

SUBMITTER: Sha L 

PROVIDER: S-EPMC9462477 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature