title: [PCSK9: Structure and function. PCSK9 and low-density lipoprotein receptor. Mutations and their effects].
abstract: Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low-density lipoprotein receptor (LDLr) and then targets it for lysosomal degradation in cells, thus preventing LDLr from recycling back to the hepatocyte surface, with a consequent decrease in LDLr density and clearance of LDL-cholesterol (LDLc). There have been reports of both gain-of-function mutations in the PCSK9 gene that cause a marked increase in LDLc conentrations and loss-of-function mutations, which lead to modest reductions in LDLc and low rates of coronary heart disease. The PCSK9 gene has become a promising therapeutic target to reduce blood cholesterol levels. This review discusses the most interesting recent data on PCSK9 regulation and its molecular function in cholesterol homeostasis.
authors.affiliation: Unitat de Lípids, Hospital del Mar, Barcelona, Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, España. Electronic address: 86620@parcdesalutmar.cat.
authors.forename: Juan
authors.initials: J
authors.lastname: Pedro-Botet
authors.affiliation: Cardiovascular Research Center (CSIC-ICCC), Institut Català de Ciències Cardiovasculars (ICCC), Hospital de la Santa Creu i Sant Pau, Barcelona, España.
authors.forename: Lina
authors.initials: L
authors.lastname: Badimón
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D003327:Coronary Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D009154:Mutation; D000071449:Proprotein Convertase 9 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism*
chemical_list: D008078:Cholesterol, LDL; D011973:Receptors, LDL; D002784:Cholesterol; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9
keywords: LDL metabolism; LDL receptor; Lipoprotein(a); Lipoproteína(a); Metabolismo LDL; PCSK9; Receptor LDL; cLDL