1. PCSK9: A Key Target for the Treatment of Cardiovascular Disease (CVD)
- Author
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Reza Parvan, Jalal Abdolalizadeh, Mahdi Edalati, Daryoush Mohammadnejad, Saeideh Sobati, Amir Shakouri, and Javad Masoumi
- Subjects
Monoclonal antibody ,Pharmaceutical Science ,Review Article ,02 engineering and technology ,030226 pharmacology & pharmacy ,LDL ,PCSK9 ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Extracellular ,Gene silencing ,General Pharmacology, Toxicology and Pharmaceutics ,Cholesterol ,lcsh:RM1-950 ,Atherosclerosis ,021001 nanoscience & nanotechnology ,Proprotein convertase ,Cell biology ,Coronary heart disease ,lcsh:Therapeutics. Pharmacology ,chemistry ,LDL receptor ,Kexin ,lipids (amino acids, peptides, and proteins) ,Sterol regulatory element-binding protein 2 ,0210 nano-technology - Abstract
Proprotein convertase subtilisin/kexin type 9 (PCSK9), as a vital modulator of low-densitylipoprotein cholesterol (LDL-C) , is raised in hepatocytes and released into plasma where it bindsto LDL receptors (LDLR), leading to their cleavage. PCSK9 adheres to the epidermal growthfactor-like repeat A (EGF-A) domain of the LDLR which is confirmed by crystallography. LDLRexpression is adjusted at the transcriptional level through sterol regulatory element bindingprotein 2 (SREBP-2) and at the post translational stages, specifically through PCSK9, and theinducible degrader of the LDLR PCSK9 inhibition is an appealing new method for reducing theconcentration of LDL-C. In this review the role of PCSK9 in lipid homeostasis was elucidated, theeffect of PCSK9 on atherosclerosis was highlighted, and contemporary therapeutic techniquesthat focused on PCSK9 were summarized. Several restoration methods to inhibit PCSK9 havebeen proposed which concentrate on both extracellular and intracellular PCSK9, and theyinclude blockage of PCSK9 production by using gene silencing agents and blockage of it’sbinding to LDLR through antibodies and inhibition of PCSK9 autocatalytic processes by tinymolecule inhibitors.
- Published
- 2020