Inclisiran is a small interfering RNA that acts as an inhibitor of a proprotein convertase, specifically, inhibiting translation of the protein termed proprotein convertase subtilisin/kexin type 9 (PCSK9).[12][4] Small interfering RNA molecules (siRNAs) are designed to intervene in the pathway of RNA interference (RNAi), a naturally operating mechanism, wherein they bind to a complex within the cell termed the RNA-induced silencing complex (RISC); after binding, the RISC structure in the siRNA-RISC complex is altered, allowing it to cleave specific messenger RNA molecules (mRNAs). The siRNA-RISC complex is catalytic, and thus can cleave multiple copies of the mRNA that it targets; cleaved mRNAs are not translated into proteins, and thus the concentration of the protein targeted by the siRNA design is decreased.
The proprotein convertase, PCSK9, is a liver-produced and -secreted serine protease whose binding and action on LDL receptors results in their increased lysosomal degradation in hepatocytes, a consequence of which is an increase in the level of circulating LDL cholesterol (and inhibition of which, the decrease in this level).
PCSK9+AND+insulin
Hepatic PCSK9 expression is regulated by nutritional status via insulin and sterol regulatory element-binding protein 1c, 2006(19)57975-3/fulltext
PCSK9 acts as a natural inhibitor of the low density lipoprotein receptor pathway, and both genes are regulated by depletion of cholesterol cell content (hypothyroidism!!!) and statins, via sterol regulatory element-binding protein (SREBP).
PCSK9 is expressed in human visceral adipose tissue and regulated by insulin and cardiac natriuretic peptides, 2019
… PCSK9 and LDLR regulation in human adipocytes. We studied PCSK9 and LDLR regulation
by insulin, atrial natriuretic peptide (ANP, a potent lipolytic agonist that antagonizes insulin),
PCSK9+AND+thyroid
Thyroid stimulating hormone exhibits the impact on LDLR/LDL-c via up-regulating hepatic PCSK9 expression, 2017
… human thyroid stimulating hormone (rhTSH) stimulated PCSK9 mRNA expression in a dose
dependent manner (A), and 25 ng/ml rhTSH increased the mRNA levels of PCSK9 both after …
