The functional rescue of novel epilepsy-linked missense mutations in the human GABA transporter 1 by pharmacochaperoning
Nikita Shah, Ameya Kasture, Thomas Hummel, Sonja Sucic* · FENS Forum 2024
The human γ-aminobutyric acid (GABA) transporter 1 (hGAT-1) is responsible for clearing GABA from synapse into neurons and astrocytes.Its mutations are known to impair protein folding and trigger epilepsy.Such folding defects are amenable to rescue by chemical and pharmacological chaperones.Our aim is to elucidate molecular features of two novel disease variants, in HEK293 cells (in vitro) and Drosophila melanogaster (in vivo).Deglycosylation experiments (endoglycosidase H(Endo H)) revealed distinct expression patterns for wild type hGAT-1 and the mutants: ER-resident proteins are core-glycosy
ePoster · Neuroscience