Inhibition of SC4MOL and HSD17B7 shifts cellular sterol composition and promotes oligodendrocyte formation
M.J. Pleshinger, Ryan M. Friedrich, Zita Hubler, Adrianna M. Rivera-León, Farrah Gao, David Yan, Joel L. Sax, Ramya Srinivasan, Ilya Bederman, H. Elizabeth Shick, Paul J. Tesar, Drew Adams
Abstract
probe of SC4MOL activity. Mechanistically, the cellular accumulation of these 8,9-unsaturated sterols represents a central driver of enhanced oligodendrocyte formation, as exogenous addition of purified SC4MOL and HSD17B7 substrates but not their 8,9-saturated analogs promotes OPC differentiation. Our work validates SC4MOL and HSD17B7 as novel targets for promoting oligodendrocyte formation, underlines a broad role for 8,9-unsaturated sterols as enhancers of oligodendrocyte formation, and establishes the first high-quality small molecules targeting SC4MOL and HSD17B7 as novel tools for probing diverse areas of biology.