Abstract
Protein homeostasis (proteostasis) relies on an orchestrated balance between protein synthesis, folding, assembly, trafficking, and degradation to ensure normal physiological function. Protein misfolding diseases often arise as a result of deficient proteostasis. Proteostasis regulators enhance the proteostasis network capacity to correct the folding, thus promoting the trafficking and restoring the function of disease-associated variants. Here, we focus on the application of proteostasis regulators to promote the folding, assembly, and trafficking of pathogenic γ-aminobutyric acid type A (GABAA) receptor variants. Since clinical variants in GABAA receptors often lead to neurological diseases, such as epilepsy, proteostasis regulators have the promise to be developed as novel therapeutics to target misfolding-prone GABAA receptors to treat their protein conformational diseases.
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