Beyond cholesterol metabolism: The pleiotropic effects of proprotein convertase subtilisin/kexin type 9 (PCSK9). Genetics, mutations, expression, and perspective for long-term inhibition.
PCSK9
dyslipidemia
familial hypercholesterolemia
low-density lipoprotein
pleiotropic effects
Journal
BioFactors (Oxford, England)
ISSN: 1872-8081
Titre abrégé: Biofactors
Pays: Netherlands
ID NLM: 8807441
Informations de publication
Date de publication:
May 2020
May 2020
Historique:
received:
11
12
2019
accepted:
11
01
2020
pubmed:
31
1
2020
medline:
23
4
2021
entrez:
31
1
2020
Statut:
ppublish
Résumé
Proprotein convertase subtilisin/kexin type 9 (PCSK9) has a crucial role in lipid metabolism, particularly due to its function in low-density lipoprotein receptor degradation. Gain-of-function genetic mutations of PCSK9 result in autosomal dominant familial hypercholesterolemia, characterized by high levels of low-density lipoprotein cholesterol (LDL-C) and clinical signs of early atherosclerosis. In recent years, PCSK9 has become an important therapeutic target for cholesterol-lowering therapy. Particularly, its inhibition with monoclonal antibodies has shown excellent efficacy in decreasing LDL-C and reducing cardiovascular events. However, PCSK9, first identified in the brain, seems to be a ubiquitous protein with different tissue-specific functions also independent of cholesterol metabolism. Accordingly, it appears to be involved in the immune response, haemostasis, glucose metabolism, neuronal survival, and several other biological functions. This review provides a comprehensive overview of the genetics, biochemical structure, expression, and function of PCSK9 and discusses the potential implications of its long-term pharmacological inhibition.
Substances chimiques
PCSK9 protein, human
EC 3.4.21.-
Proprotein Convertase 9
EC 3.4.21.-
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
367-380Informations de copyright
© 2020 International Union of Biochemistry and Molecular Biology.
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