|
4-Phenylbutyric acid (PBA) and tauroursodeoxycholic acid (TUDCA)
|
Chemical chaperones: stabilize protein conformation during folding, ameliorate trafficking of mutant proteins, suppress unfolded protein aggregation
| |
[71]
|
|
Dantrolene
|
Blocks ryanodine receptor in the ER membrane: stabilize ER calcium level by suppressing the efflux of calcium from ER to cytosol
|
Clinical trial of dantrolene sodium in pediatric and adult patients with WS, ClinicalTrials.gov: NCT02829268
|
[28, 72, 74]
|
|
Pioglitazone
|
Inhibits inositol triphosphate (IP3R)-mediated release of calcium from the ER
| |
[45, 75,76,77,78]
|
|
Rapamycin
|
Reduces cytoplasmic calcium by a mechanism similar to pioglitazone
| |
[76]
|
|
Carbachol
|
Muscarinic receptor 3 (M3) agonist: mobilizes intracellular calcium stores and potentiates glucose-stimulated insulin secretion
| |
[79, 80]
|
|
Liraglutide, exenatide, semaglutide
|
Glucagon-like peptide-1 receptor (GLP-1R) agonists. They activate PERK-ATF4 pathway and interfere with the ER unfolded protein response
| |
[28, 81,82,83,84,85,86]
|
|
Sitagliptin, vildagliptin, gemigliptin
|
Inhibitors of dipeptidyl peptidase-4 (DPP-4), an enzyme that deactivates GLP-1, thus also increasing GLP-1 levels
| |
[71]
|
|
Salubrinal
|
Selective inhibitor of the eIF2α phosphatase
| |
[87, 88]
|
|
Valproate acid (VPA)
|
Promotes the expression of both WFS1 and ER chaperones and attenuates ER-induced apoptosis
|
Efficacy and safety trial of sodium valproate in pediatric and adult patients with WS, ClinicalTrials.gov: NCT03717909
|
[89,90,91,92,93,94]
|
