Pharmacological activation of ATF6 remodels the proteostasis network to rescue pathogenic GABA_A receptors.

ABSTRACT:

Background

Genetic variants in the subunits of the gamma-aminobutyric acid type A (GABA_A) receptors are implicated in the onset of multiple pathologic conditions including genetic epilepsy. Previous work showed that pathogenic GABA_A subunits promote misfolding and inefficient assembly of the GABA_A receptors, limiting receptor expression and activity at the plasma membrane. However, GABA_A receptors containing variant subunits can retain activity, indicating that enhancing the folding, assembly, and trafficking of these variant receptors offers a potential opportunity to mitigate pathology associated with genetic epilepsy.

Results

Here, we demonstrate that pharmacologically enhancing endoplasmic reticulum (ER) proteostasis using smal

SUBMITTER: Wang M 

PROVIDER: S-EPMC9044816 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature