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ID: ALA3352343
Journal: Bioorg Med Chem Lett
Title: Structure-activity relationships of oxysterol-derived pharmacological chaperones for Niemann-Pick type C1 protein.
Authors: Ohgane K, Karaki F, Noguchi-Yachide T, Dodo K, Hashimoto Y.
Abstract: Niemann-Pick disease type C is a fatal neurodegenerative disease, and its major cause is mutations in NPC1 gene. This gene encodes NPC1 protein, a late endosomal polytopic membrane protein required for intracellular cholesterol trafficking. One prevalent mutation (I1061T) has been shown to cause a folding defect, which results in failure of endosomal localization of the protein, leading to loss-of-function phenotype. We have previously demonstrated that several oxysterols and their derivatives act as pharmacological chaperones; binding of these compounds to NPC1(I1061T) mutant protein corrects the localization/maturation defect of the mutant protein. Here, we disclose detailed structure-activity relationships of oxysterol derivatives as pharmacological chaperones for NPC1(I1061T) mutant.
CiteXplore: 24928400