PCSK9 enhances LDL cholesterol (LDL-c) levels by escorting the liver LDL receptor (LDLR) to endosomes and lysosomes for degradation. PCSK9 monoclonal antibodies and RNA-antisense formulations are effective in reducing LDL cholesterol in patients. The recent structural identification of a novel pocket in PCSK9 paves the way to the future development of orally active small-molecule hypocholesterolemic drugs.
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Acknowledgements
This work was supported by the CIHR grants Foundation Scheme #148363, a Canada Research Chair #231335, and a Fondation Leducq grant #13CVD03. The author acknowledges the expert contribution of E. Girard.
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Seidah, N. Insights into a PCSK9 structural groove: a harbinger of new drugs to reduce LDL-cholesterol. Nat Struct Mol Biol 24, 785–786 (2017). https://doi.org/10.1038/nsmb.3471
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DOI: https://doi.org/10.1038/nsmb.3471