Topic
Sterol
About: Sterol is a research topic. Over the lifetime, 8117 publications have been published within this topic receiving 309926 citations. The topic is also known as: sterols & sterol lipids.
Papers published on a yearly basis
Papers
More filters
TL;DR: The identified SIRT2 inhibitor reduced cholesterol in cultured naïve neuronal cells and brain slices from wild-type mice and provides a clear opportunity for lead optimization and drug development, targeting metabolic dysfunctions in CNS disorders where abnormal cholesterol homeostasis is implicated.
Abstract: Sirtuin 2 (SIRT2) deacetylase-dependent inhibition mediates neuroprotective reduction of cholesterol biosynthesis in an in vitro Huntington's disease model. This study sought to identify the first brain-permeable SIRT2 inhibitor and to characterize its cholesterol-reducing properties in neuronal models. Using biochemical sirtuin deacetylation assays, we screened a brain-permeable in silico compound library, yielding 3-(1-azepanylsulfonyl)-N-(3-bromphenyl)benzamide as the most potent and selective SIRT2 inhibitor. Pharmacokinetic studies demonstrated brain-permeability but limited metabolic stability of the selected candidate. In accordance with previous observations, this SIRT2 inhibitor stimulated cytoplasmic retention of sterol regulatory element binding protein-2 and subsequent transcriptional downregulation of cholesterol biosynthesis genes, resulting in reduced total cholesterol in primary striatal neurons. Furthermore, the identified inhibitor reduced cholesterol in cultured naive neuronal cells and brain slices from wild-type mice. The outcome of this study provides a clear opportunity for lead optimization and drug development, targeting metabolic dysfunctions in CNS disorders where abnormal cholesterol homeostasis is implicated.
122 citations
TL;DR: The phyla-specific residue can be used to predict preferred substrates of new CYP51 sequences and subsequently for the development of new artificial substrate analogs, which might serve as highly specific inhibitors able to kill human parasites.
122 citations
TL;DR: The phytosterol compositions in unsaponifiables of fig (Ficus carica, var. Mission) fruit and 3 structural components of the branches; and the fatty acid composition of fig fruits were studied using gas chromatography/mass spectrometry.
Abstract: The phytosterol compositions in unsaponifiables of fig (Ficus carica, var. Mission) fruit and 3 structural components of the branches; and the fatty acid composition of fig fruits were studied using gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS). The phytosterols were determined from the trimethylsilyl ether (TMS) derivatives of the unsaponifiable samples. Fourteen compounds were separated from fig fruit; 13, 10, and 6 in bark, stem, and pith, respectively. Sitosterol was the most predominant sterol in all parts. Also detected were campesterol, stigmasterol, and fucosterol. Fatty acids in fig fruit, determined as their methyl esters, were myristic (14:0), palmitic (16:0), stearic (18:0), oleic (18:1), linoleic (18:2), and linolenic (18:3) acids.
122 citations
TL;DR: StAR is a cholesterol-binding protein, preferentially enhances sterol transfer from steroidogenic cell mitochondria, and interacts with mitochondrial membranes to alter their sterol domain structure and dynamics.
122 citations
TL;DR: In summary, the erg4Δ and erg6Δ mutants exhibited the most compromised phenotypes, and as Erg6p is not involved in the cholesterol biosynthetic pathway, it may become a target for a new generation of antifungal drugs.
Abstract: We investigated the impact of the deletions of genes from the final steps in the biosynthesis of ergosterol (ERG6, ERG2, ERG3, ERG5, ERG4) on the physiological function of the Saccharomyces cerevisiae plasma membrane by a combination of biological tests and the diS-C3(3) fluorescence assay. Most of the erg mutants were more sensitive than the wild type to salt stress or cationic drugs, their susceptibilities were proportional to the hyperpolarization of their plasma membranes. The different sterol composition of the plasma membrane played an important role in the short-term and long-term processes that accompanied the exposure of erg strains to a hyperosmotic stress (effect on cell size, pH homeostasis and survival of yeasts), as well as in the resistance of cells to antifungal drugs. The pleiotropic drug-sensitive phenotypes of erg strains were, to a large extent, a result of the reduced efficiency of the Pdr5 efflux pump, which was shown to be more sensitive to the sterol content of the plasma membrane than Snq2p. In summary, the erg4Δ and erg6Δ mutants exhibited the most compromised phenotypes. As Erg6p is not involved in the cholesterol biosynthetic pathway, it may become a target for a new generation of antifungal drugs.
122 citations