Itraconazole and posaconazole, inhibitors of NPC1 sterol transport, act as pharmacological chaperones after washout.

ABSTRACT: Niemann-Pick type C (NPC) disease is a rare lysosomal storage disorder primarily caused by mutations in the NPC Cholesterol Transporter 1 (NPC1) gene, resulting in cholesterol and lipid accumulation in late endosomes and lysosomes. While several therapeutic drugs show promise in reducing cholesterol accumulation, none of the current treatments are highly effective. Itraconazole and posaconazole, widely used antifungal drugs, have been shown to stabilize misfolded NPC1 proteins, enabling their escape from endoplasmic reticulum-associated degradation. This chaperone-like property makes them attractive candidates for testing chaperones as possible treatments for NPC disease, but both drugs also inhibit NPC1 function. In this study, we employed a washout approach to reverse the inhibitory effe

SUBMITTER: Wang WA 

PROVIDER: S-EPMC12272866 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature