Modulation of lanosterol synthase drives 24,25-epoxysterol …
网页2021年6月17日 · This work highlights epoxycholesterol shunt usage, controlled by inhibitors of LSS, as a target to promote oligodendrocyte formation. Additionally, sterols beyond the 8,9-unsaturated sterols, including 24,25 …
Lanosterol synthase - Wikipedia
网页Lanosterol synthase inhibitors are thought to lower LDL and VLDL cholesterol by a dual control mechanism. Studies in which lanosterol synthase is partially inhibited have shown both a direct decrease in lanosterol formation and a …
Selective and brain-penetrant lanosterol synthase inhibitors …
网页2023年2月8日 · Here we report a brain-penetrant, highly selective LSS inhibitor for which in vivo administration led to no detectable EPC production in normal brain but dose-dependent increases in EPC in orthotopic GBM tumors. Our report provides a starting point for the development of optimized brain-bioavailable LSS inhibitors to enable efficacy studies in ...
Target identification reveals lanosterol synthase as a vulnerability …
网页2019年4月4日 · Partial inhibition of LSS promotes flux through the shunt pathway, which results in the combinatorial effect of increasing 24,25 epoxycholesterol, which activates LXR-mediated cholesterol export while concurrently …
Chemical Inhibition of Sterol Biosynthesis - PMC - National Center …
网页2024年3月28日 · The primary function of LSS is to convert 2,3-oxidosqualene into lanosterol [108,109]. LSS mutations have been associated with cataracts (OMIM 600909 ), hypotrichosis (OMIM 618275 ) in affected children, and a phenotype referred to as alopecia-intellectual disability syndrome-4 (OMIM 618840 ) [113,114].
Lanosterol reverses protein aggregation in cataracts - Nature
网页2015年7月22日 · Co-expression of wild-type LSS and a cataract-causing mutant crystallin protein significantly reduced both the number and size of intracellular crystallin aggregates, whereas LSS mutants failed...
网页2023年2月9日 · MM0299 inhibits lanosterol synthase (LSS) and diverts sterol flux away from cholesterol into a ‘‘shunt’’ pathway that culminates in 24(S),25-epoxycholesterol (EPC). EPC synthesis following MM0299 treatment is both necessary and sufficient to block the growth of mouse
Selective and brain-penetrant lanosterol synthase inhibitors …
网页2023年2月16日 · MM0299 inhibits lanosterol synthase (LSS) and diverts sterol flux away from cholesterol into a "shunt" pathway that culminates in 24 (S),25-epoxycholesterol (EPC). EPC synthesis following MM0299 treatment is both necessary and sufficient to block the growth of mouse and human glioma stem-like cells by depleting cellular cholesterol.
Lanosterol Synthase Pathway Alleviates Lens Opacity in Age …
网页2018年7月11日 · LSS expression was analyzed by western blot and enzyme-linked immunosorbent assay (ELISA). To further examine the function of LSS, we used U18666A, an LSS inhibitor in rat lens culture system. Results: In lens epithelial cells (LECs), LSS expression in LECs increased with opaque degree C II, while it decreased with opaque degree C IV and C V ...
Target identification reveals lanosterol synthase as a ... - PNAS
网页Partial inhibition of LSS promotes flux through the shunt pathway, which results in the combinatorial effect of increasing 24,25 epoxycholesterol, which activates LXR-mediated cholesterol export while concurrently reducing postoxidosqualene cholesterol synthesis.